Heterocyclic compounds having hypolipidemic, hypocholesteremic activities process for their preparation and pharmaceutical compositions containing them and their use in medicine

ABSTRACT

Novel β-aryl-α-substituted propanoic acids having hypolipidemic and hypocholesteremic activities.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation-in-part patent application of U.S.patent application Ser. No. 09/928,242, filed on Aug. 10, 2001 nowabandoned.

FIELD OF INVENTION

The present invention relates to novel hypolipidaemic andhypocholesterolemic compounds, their derivatives, their analogs, theirtautomeric forms, their stereoisomers, their polymorphs, theirpharmaceutically acceptable salts, their pharmaceutically acceptablesolvates and pharmaceutically acceptable compositions containing them.More particularly, the present invention relates to novelβ-aryl-α-substituted propanoic acids of the general formula (I), theirderivatives, their analogs, their tautomeric forms, their stereoisomers,their pharmaceutically acceptable salts, their pharmaceuticallyacceptable solvates, pharmaceutical compositions containing them, use ofthese compounds in medicine and the intermediates involved in theirpreparation.

The present invention also relates to a process for the preparation ofthe above said novel compounds, their derivatives, their analogs, theirtautomeric forms, their stereoisomers, their pharmaceutically acceptablesalts, their pharmaceutically acceptable solvates, and pharmaceuticalcompositions containing them.

The compounds of the general formula (I) lower or modulate triglyceridelevels and/or cholesterol levels and/or low-density lipoproteins (LDL)and raise HDL plasma levels and hence are useful in combating differentmedical conditions, where such lowering (and raising) is beneficial.Thus, it could be used in the treatment and/or prophylaxis of obesity,hyperlipidaemia, hypercholesteremia, hypertension, atheroscleroticdisease events, vascular restenosis, diabetes and many other relatedconditions.

The compounds of general formula (I) are useful to prevent or reduce therisk of developing atherosclerosis, which leads to diseases andconditions such as artereosclerotic cardiovascular diseases, stroke,coronary heart diseases, cerebrovascular diseases, peripheral vesseldiseases and related disorders. These compounds of general formula (I)are useful for the treatment and/or prophylaxis of metabolic disordersloosely defined as Syndrome X. The characteristic features of Syndrome Xinclude initial insulin resistance followed by hyperinsulinemia,dyslipidemia and impaired glucose tolerance. The glucose intolerance canlead to non-insulin dependent diabetes mellitus (NIDDM, Type 2diabetes), which is characterized by hyperglycemia, which if notcontrolled may lead to diabetic complications or metabolic disorderscaused by insulin resistance. Diabetes is no longer considered to beassociated only with glucose metabolism, but it affects anatomical andphysiological parameters, the intensity of which vary depending uponstages/duration and severity of the diabetic state. The compounds ofthis invention are also useful in prevention, halting or slowingprogression or reducing the risk of the above mentioned disorders alongwith the resulting secondary diseases such as cardiovascular diseases,like arteriosclerosis, atherosclerosis; diabetic retinopathy, diabeticneuropathy and renal disease including diabetic nephropathy,glomerulonephritis, glomerular sclerosis, nephrotic syndrome,hypertensive nephrosclerosis and end stage renal diseases, likemicroalbuminuria and albuminuria, which may be result of hyperglycemiaor hyperinsulinemia.

The compounds of the present invention can be useful as aldose reductaseinhibitors; for improving cognitive functions in dementia, and in thetreatment and/or prophylaxis of disorders such as psoriasis, polycysticovarian syndrome (PCOS), cancer, osteoporosis, leptin resistance,inflammation and inflammatory bowel diseases, xanthoma, pancreatitis,myotonic dystrophy, endothelial cell dysfunction and hyperlipidemia.

The compounds of the present invention are useful in the treatment ofthe diseases mentioned herein, alone or in combination one or morehypoglycemic, antihyperglycemic, hypolipidaemic, hypolipoproteinemicagents, antioxidants, antihypertensives, such as HMG CoA reductaseinhibitor, fibrate, statins, glitazones, sulfonyl ureas, insulin,α-glycosidase inhibitors, nicotinic acid, cholestyramine, cholestipol orprobucol, and the like.

BACKGROUND OF THE INVENTION

Hyperlipidaemia has been recognized as the major risk factor in causingcardiovascular diseases due to atherosclerosis. Atherosclerosis andother such peripheral vascular diseases affect the quality of life of alarge population in the world. The therapy aims to lower the elevatedplasma LDL cholesterol, low-density lipoprotein and plasma triglyceridesin order to prevent or reduce the risk of occurrence of cardiovasculardiseases. The detailed etiology of atherosclerosis and coronary arterydiseases is discussed by Ross and Glomset [New Engl. J. Med., 295,369–377 (1976)]. Plasma cholesterol is generally found esterified withvarious serum lipoproteins and numerous studies have suggested aninverse relationship between serum HDL-cholesterol level and risk foroccurrence of cardiovascular disease. Many studies have suggested anincreased risk of coronary artery diseases (CAD) due to elevated LDL andVLDL-cholesterol levels [Stampfer et al., N. Engl. J. Med., 325,373–381(1991)]. The other studies illustrate protective effects of HDLagainst progression of atherosclerosis. Thus, HDL has become a crucialfactor in treating diseases with increased levels of cholesterol [Milleret. al., Br. Med. J. 282, 1741–1744(1981); Picardo et al.,Arteriosclerosis, 6, 434–441 (1986); Macikinnon et al., J. Biol. Chem.261, 2548–2552 (1986)].

Diabetes is associated with a number of complications and also affect alarge population. This disease is usually associated with other diseasessuch as obesity, hyperlipidemia, hypertension and angina. It is wellestablished that improper treatment can aggravate impaired glucosetolerance and insulin resistance, thereby leading to frank diabetes.Further, patients with insulin resistance and type 2 diabetes often haveraised triglycerides and low HDL-cholesterol concentrations andtherefore, have greater risk of cardiovascular diseases. The presenttherapy for these diseases includes sulfonylureas and biguanides alongwith insulin. This type of drug therapy may lead to mild to severehypoglycemia, which may lead to coma or in some cases may lead to death,as a result of unsatisfactory glycaemic control by these drugs. Recentaddition of drugs in the treatment of diabetes are thethiazolidinediones, drugs having insulin-sensitizing action.Thiazolidinediones are prescribed alone or in combination with otheranti-diabetic agents like troglitazone, rosiglitazone and pioglitazone.These are useful in treating diabetes, lipid metabolism but aresuspected to have tumor-inducing potential and cause hepaticdysfunction, which may lead to liver failure. Further, seriousundesirable side-effects have occurred in animal and/or human studieswhich include cardiac hypertrophy, hema dilution and liver toxicity in afew glitazones progressing to advanced human trials. The drawback isconsidered to be idiosyncratic. Presently, there is a need for a safeand an effective drug, to treat insulin resistance, diabetes andhyperlipidemia. [Exp. Clin. Endocrinol. Diabetes: 109(4), S548–9 (2001)]

Obesity is another major health problem being associated with increasedmorbidity and mortality. It is a metabolic disorder, in which excess offat is accumulated in the body. Although, its etiology is unclear, thegeneral feature includes excess of calorie intake than it is consumed.Various therapies such as dieting, exercise, appetite suppression,inhibition of fat absorption etc. have been used to combat obesity.However, more efficient therapies to treat this abnormality is essentialas obesity is closely related to several diseases such as coronary heartdisease, stroke, diabetes, gout, osteoarthritis, hyperlipidaemia andreduced fertility. It also leads to social and psychological problems[Nature Reviews: Drug Discovery: 1(4), 276–86 (2002)].

Peroxisome Proliferator Activated Receptor (PPAR) is a member of thesteroid/retinoid/thyroid hormone receptor family. PPAR∝, PPARγ and PPARδhave been identified as subtypes of PPARs. Extensive reviews regardingPPAR, their role in different diseased conditions are widely published[Endocrine Reviews, 20(5), 649–688 (1999); J. Medicinal Chemistry,43(4), 58–550 (2000); Cell, 55, 932–943 (1999); Nature, 405, 421–424(2000); Trends in Pharmacological Sci., 469–473 (2000)]. PPARγactivation has been found to play a central role in initiating andregulating adipocyte differentiation [Endocrinology 135, 798–800,(1994)] and energy homeostasis, [Cell, 83, 803–812 (1995); Cell, 99,239–242 (1999)]. PPARγ agonists would stimulate the terminaldifferentiation of adipocyte precursors and cause morphological andmolecular changes characteristic of a more differentiated, lessmalignant state. During adipocyte differentiation, several highlyspecialized proteins are induced, which are being involved in lipidstorage and metabolism. It is accepted that PPARγ activation leads toexpression of CAP gene [Cell biology, 95, 14751–14756, (1998)], however,the exact link from PPARγ activation to changes in glucose metabolismand decrease in insulin resistance in muscle has not been clear. PPARαis involved in stimulating β-oxidation of fatty acids [Trends Endocrine.Metabolism, 4, 291–296 (1993)] resulting in plasma circulating freefatty acid reduction [Current Biol., 5, 618–621 (1995)]. Recently, roleof PPARγ activation in the terminal differentiation of adipocyteprecursors has been implicated in the treatment of cancer. [Cell, 79,1147–1156 (1994); Cell, 377–389 (1996); Molecular Cell, 465–470)1998);Carcinogenesis, 1949–1953 (1998); Proc. Natl. Acad. Sci., 94, 237–241(1997); Cancer Research, 58, 3344–3352 (1998)]. Since PPARγ is expressedin certain cells consistently, PPARγ agonists would lead to nontoxicchemotherapy. There is growing evidence that PPAR agonists may alsoinfluence the cardiovascular system through PPAR receptors as well asdirectly by modulating vessel wall function [Med. Res. Rev., 20 (5),350–366 (2000)].

PPAR α agonists have been found useful in the treatment of obesity (WO97/36579). Dual PPAR α and γ agonists have been suggested to be usefulfor Syndrome X (WO 97/25042). PPAR γ agonists and HMG-CoA reductaseinhibitors have exhibited synergism and indicated the usefulness of thecombination in the treatment of atherosclerosis and xanthoma (EP 0753298).

Leptin is a protein when bound to leptin receptors is involved insending satiety signal to the hypothalamus. Leptin resistance wouldtherefore lead to excess food in-take, reduced energy expenditure,obesity, impaired glucose tolerance and diabetes [Science, 269,543–46(1995)]. It has been reported that insulin sensitizers lowerplasma leptin concentration [Proc. Natl. Acad. Sci. 93, 5793–5796(1996): WO 98/02159)].

A number of compounds belonging to β-aryl-α-hydroxypropanoic acids andtheir derivatives have been reported to be useful in the treatment ofhyperlipidemia, hypercholesterolemia and hyperglycemia [U.S. Pat. Nos.5,306,726, 5,985,884, 6,054,453, 6,130,214, EP 90 3343, PCT publicationsNos. WO 91/19702, WO 94/01420, WO 94/13650, WO 95/03038, WO 95/17394, WO96/04260, WO 96/04261, WO 96/33998, WO 97/25042, WO 97/36579, WO98/28534, WO 99/08501, WO 99/16758, WO 99/19313, WO99/20614, WO00/23417, WO 00/23445, WO 00/23451, WO 01/53257].

A few β-aryl-α-hydroxypropanoic acids, their derivatives, and theiranalogs have been reported to be useful in the treatment ofhyperglycemia and hypercholesterolemia. Some of such compounds describedin the prior art are outlined below:

-   U.S. Pat. Nos. 5,306,726 and 5,089,514 disclose several    3-aryl-2-hydroxypropionic acid derivatives of general formulae (II)    and (III) as hypolipidaemic and hypoglycemic agents. Examples of    these compounds are shown in the formulae (IV) and (V).

-   International Patent Applications, U.S. Pat. No. 6,166,049 and WO    96/04260 disclose compounds of general formula (VI) wherein, R^(a)    represents 2-benzoxazolyl or 2-pyridyl and R^(b) represent CF₃,    CH₂OCH₃ or CH₃. A typical example is    (S)-3-[4-[2-[N-(2-benzoxazolyl)N-methylamino]ethoxy]    phenyl]-2-(2,2,2,-trifluoro ethoxy)propanoic acid (VII).

-   International patent applications, WO 94/13650, WO 94/29302, U.S.    Pat. No. 6,048,883, WO 95/17394 and WO 97/31970 disclose the    compounds of general formula (VIII) wherein,    A¹—X—(CH₂)_(n)—O—A²—A³—YR²  (VIII)    A¹ represents aromatic heterocycle moiety, A² represents substituted    benzene ring and A³ represents moiety of formula (CH₂)_(m)—CH—(OR¹),    where R¹ represents alkyl groups, m is integer of the range of 1–5;    X represents substituted or unsubstituted N; Y represents C═O or C═S    and R² represents OR³ where R³ may be hydrogen, alkyl, aralkyl, or    aryl group and n is integer in the range of 2–6. An example of these    compounds is shown in formula (IX).

-   International patent application, WO 00/23,445, WO 00/23,417 and WO    00/23,451 disclose cyclic compounds of the general formula (X)    useful in treatment of diabetes and obesity. A typical example of    these compounds is shown formulae (XI) and (XII).

-   International patent application, WO 99/08501 and WO 97/319707,    disclose cyclic compounds of the formulae (XIII) and (XIV) active as    PPAR-gamma agonist. A typical examples of these compounds is shown    formulae (XV) and (XVI).

-   U.S. Pat. No. 6,054,453 and WO 99/16758 reports compounds of general    formulae (XVII), (XVIII), which reduce glucose, cholesterol and    triglycerides exemplified by compounds of formula (XIX).

-   WO 99/19,313, U.S. Pat. No. 6,130,214 and WO 99/38850 reports    compounds of general formula (XX) and (XXI) and (XXII) which reduce    glucose, cholesterol and triglycerides.

SUMMARY OF INVENTION

The objective of this invention is to develop novel compoundsrepresented by the general formula (I) used as hypocholesterolemic,hypolipidaemic, hypolipoproteinemic, anti-obesity and antihyperglycemicagents which may have additional body weight lowering effect andbeneficial effect in the treatment and/or prophylaxis of diseases causedby hyperlipidaemia, diseases classified under syndrome X andatherosclerosis.

The main objective of the present invention is to provide novelβaryl-α-substituted propanoic acids represented by the general formula(I), their derivatives, their analogs, their tautomeric forms, theirstereoisomers, their polymorphs, their pharmaceutically acceptablesalts, their pharmaceutically acceptable solvates, and pharmaceuticalcompositions containing them or their mixtures thereof.

Another objective of the present invention is to provide novelβ-aryl-α-substituted propanoic acids represented by the general formula(I), their derivatives, their analogs, their tautomeric forms, theirstereoisomers, their pharmaceutically acceptable salts, theirpharmaceutically acceptable solvates, and pharmaceutical compositionscontaining them or their mixtures thereof having enhanced activities,without toxic effects or with reduced toxic effect.

Yet another objective of this invention is to provide a process for thepreparation of novel β-aryl-α-substituted propanoic acids represented bythe general formula (I), their derivatives, their analogs, theirtautomeric forms, their stereoisomers, their pharmaceutically acceptablesalts, their pharmaceutically acceptable solvates.

Still another objective of the present invention is to providepharmaceutical compositions containing compounds of the general formula(I), their derivatives, their analogs, their tautomeric forms, theirstereoisomers, their pharmaceutically acceptable salts, theirpharmaceutically acceptable solvates or their mixtures in combinationwith suitable carriers, solvents, diluents and other media normallyemployed in preparing such compositions.

A further objective of the present invention is to provide process forpreparation of intermediates involved in the process.

DETAILED DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to compounds of the generalformula (I),

their derivatives, their analogs, their tautomeric forms, theirstereoisomers, their polymorphs, their pharmaceutically acceptablesalts, their pharmaceutically acceptable solvates, wherein R¹, R², R³,R⁴ may be same or different, and represent

-   hydrogen, halogen, haloalkyl, perhaloalkyl, haloalkoxy,    perhaloalkoxy, hydroxy, thio, amino, nitro, cyano, formyl, amidino,    guanidino,-   or substituted or unsubstituted groups selected from-   linear or branched (C₁–C₁₂)alkyl, linear or branched    (C₁–C₁₂)alkenyl, linear or branched (C₁–C₁₂)alkynyl,    (C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl, bicycloalkyl,    bicycloalkenyl, (C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy,    cyclo(C₃–C₇)alkoxy, aryl, aryloxy, aralkyl, ar(C₁–C₁₂)alkoxy,    heterocyclyl, heteroaryl, heterocyclyl(C₁–C₁₂)alkyl,    heteroar(C₁–C₁₂)alkyl, heteroaryloxy, heteroar(C₁–C₁₂)alkoxy,    heterocycloxy, heterocyclylalkyloxy,-   acyl, acyloxy, acylamino, mono-substituted or di-substituted amino,    arylamino, aralkylamino,-   carboxylic acid and its derivatives such as esters and amides,-   hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted    aminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl,-   (C₁–C₁₂)alkylthio, thio(C₁–C₁₂)alkyl, arylthio,-   (C₁–C₁₂)alkoxycarbonylamino, aryloxycarbonylamino,    aralkyloxycarbonylamino, aminocarbonylamino,    alkylaminocarbonylamino, alkylamidino, alkylguanidino,    dialkylguanidino, hydrazino, alkyl hydrazino, alkoxyamino, hydroxyl    amino,-   derivatives of sulfenyl and sulfonyl groups,-   sulfonic acid and its derivatives,-   phosphonic acid and its derivatives;-   n represents an integer varying from 1 to 8;-   W represents O, S or NR⁹, where R⁹ represents hydrogen,    (C₁–C₁₂)alkyl or aryl groups;-   Ar represents a substituted or unsubstituted divalent single or    fused aromatic, heteroaromatic or a heterocyclic group;-   R⁵ and R⁶ represent both hydrogen or together represent a bond or    may also represent a hydroxy, (C₁–C₁₂)alkyl, (C₁–C₁₂)alkoxy,    halogen, acyl, substituted or unsubstituted aralkyl group;-   X represent O or S;-   R⁷ represents hydrogen, perfluoro(C₁–C₁₂)alkyl, substituted or    unsubstituted groups selected from linear or branched (C₁–C₁₂)alkyl,    cyclo(C₁–C₁₂)alkyl, aryl, ar(C₁–C₁₂)alkyl, heteroaryl,    heteroar(C₁–C₁–₁₂)alkyl, heterocyclyl, alkoxyalkyl, aryloxyalkyl,    alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl,    alkylaminocarbonyl, arylaminocarbonyl or acyl groups;-   Y represents O or S;-   Z represents O, S or NR¹⁰ where R¹⁰ represents hydrogen or    substituted or unsubstituted groups selected from (C₁–C₁₂) alkyl,    aryl, ar(C₁–C₁₂)alkyl, hydroxy(C₁–C₁₂)alkyl, amino(C₁–C₁₂)alkyl,    heteroaryl or heteroar(C₁–C₁₂)alkyl groups;-   R⁸ represents hydrogen, substituted or unsubstituted groups selected    from linear or branched (C₁–C₁₂)alkyl, aryl, ar(C₁–C₁₂)alkyl,    heteroaryl, heteroar(C₁–C₁₂)alkyl, heterocylyl, heterocyclylalkyl,    hydroxyalkyl, alkoxyalkyl or alkylaminoalkyl groups;-   R⁸ and R⁸ together may form 5 or 6 membered substituted or    unsubstituted heterocyclic ring structure containing one or more    heteroatoms selected from O, N or S.

The various groups, radicals and substituents used anywhere in thespecification are described in the following paragraphs.

The term “alkyl” used herein, either alone or in combination with otherradicals, denotes a linear or branched radical containing one to twelvecarbons, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl,sec-butyl, tert-butyl, amyl, t-amyl, n-pentyl, n-hexyl, iso-hexyl,heptyl, octyl and the like.

The term “alkenyl” used herein, either alone or in combination withother radicals, denotes a linear or branched radical containing one totwelve carbons; such as vinyl, allyl, 2-butenyl, 3-butenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl and the like.The term “alkenyl” includes dienes and trienes of straight and branchedchains.

The term “alkynyl” used herein, either alone or in combination withother radicals, denotes a linear or branched radical containing one totwelve carbons, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl,2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl,1-hexynyl, 3-hexynyl, 4-hexynyl, 5- hexynyl, and the like. The term“alkynyl” includes di- and tri-ynes.

The term “cyclo(C₃–C₇)alkyl” used herein, either alone or in combinationwith other radicals, denotes a radical containing three to sevencarbons, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl and the like.

The term “cyclo(C₃–C₇)alkenyl” used herein, either alone or incombination with other radicals, denotes a radical containing three toseven carbons, such as cyclopropenyl, 1-cyclobutenyl, 2-cylobutenyl,1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl,2-cyclohexenyl, 3-cyclohexenyl, 1-cycloheptenyl, cycloheptadienyl,cycloheptatrienyl, and the like.

The term “alkoxy” used herein, either alone or in combination with otherradicals, denotes a radical alkyl, as defined above, attached directlyto an oxygen atom, such as methoxy, ethoxy, n-propoxy, iso-propoxy,n-butoxy, t-butoxy, iso-butoxy, pentyloxy, hexyloxy, and the like.

The term “alkenoxy” used herein, either alone or in combination withother radicals, denotes an alkenyl radical, as defined above, attachedto an oxygen atom, such as vinyloxy, allyloxy, butenoxy, pentenoxy,hexenoxy, and the like.

The term “cyclo(C₃–C₇)alkoxy” used herein, either alone or incombination with other radicals, denotes a radical containing three toseven carbon atoms, such as cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and the like.

The term “halo” or “halogen” used herein, either alone or in combinationwith other radicals, such as “haloalkyl”, “perhaloalkyl” etc refers to afluoro, chloro, bromo or iodo group. The term “haloalkyl” denotes aradical alkyl, as defined above, substituted with one or more halogenssuch as perhaloalkyl, more preferably, perfluoro(C₁–C₆)alkyl such asfluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl,difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl,ethyl, propyl, butyl, pentyl or hexyl groups. The term “haloalkoxy”denotes a haloalkyl, as defined above, directly attached to an oxygenatom, such as fluoromethoxy, chloromethoxy, fluoroethoxy chloroethoxygroups, and the like. The term “perhaloalkoxy” denotes a perhaloalkylradical, as defined above, directly attached to an oxygen atom,tritluoromethoxy, trifluoroethoxy, and the like.

The term “aryl” or “aromatic” used herein, either alone or incombination with other radicals, denotes an aromatic system containingone, two or three rings wherein such rings may be attached together in apendant manner or may be fused, such as phenyl, naphthyl,tetrahydronaphthyl, indane, biphenyl, and the like. The term ‘aralkyl”denotes an alkyl group, as defined above, attached to an aryl, such asbenzyl, phenethyl, naphthylmethyl, and the like. The term “aryloxy”denotes an aryl radical, as defined above, attached to an alkoxy group,such as phenoxy, naphthyloxy and the like, which may be substituted. Theterm “aralkoxy” denotes an arylalkyl moiety, as defined above, such asbenzyloxy, phenethyloxy, naphthylmethyloxy, phenylpropyloxy, and thelike, which may be substituted.

The term “heterocyclyl” or “heterocyclic” used herein. either alone orin combination with other radicals, denotes saturated, partiallysaturated and unsaturated ring-shaped radicals, the heteroatoms selectedfrom nitrogen, sulfur and oxygen. Examples of saturated heterocyclicradicals include aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl,piperidinyl, piperazinyl, 2-oxopiperidinyl, 4-oxopiperidinyl,2-oxopiperazinyl, 3-oxopiperazinyl, morpholinyl, thiomorpholinyl,2-oxomorpholinyl, azepinyl, diazepinyl, oxapinyl, thiazepinyl,oxazolidinyl, thiazolidinyl, and the like; examples of partiallysaturated heterocyclic radicals include dihydrothiophene, dihydropyran,dihydrofuran, dihydrothiazole, and the like.

The term “heteroaryl” or “heteroaromatic” used herein, either alone orin combination with other radicals, denotes unsaturated 5 to 6 memberedheterocyclic radicals containing one or more hetero atoms selected fromO, N or S, attached to an aryl group, such as pyridyl, thienyl, furyl,pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, oxadiazolyl,tetrazolyl, benzopyranyl, benzofuranyl, benzothienyl, indolinyl,indolyl, azaindolyl, azaindoliiyl, quinolinyl, pyrimidinyl, pyrazolyl,quinazolinyl, pyrimidonyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl,benzothiazinonyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, and thelike.

The term “heterocyclyl(C₁–C₁₂)alkyl” used herein, either alone or incombination with other radicals, represents a heterocyclyl group, asdefined above, substituted with an alkyl group of one to twelve carbons,such as pyrrolidinealkyl, piperidinealkyl, morpholinealkyl,thiomorpholinealkyl, oxazolinealkyl, and the like, which may besubstituted. The term “heteroaralkyl” used herein, either alone or incombination with other radicals, denotes a heteroaryl group, as definedabove, attached to a straight or branched saturated carbon chaincontaining 1 to 6 carbons, such as (2-furyl)methyl, (3-furyl)methyl,(2-thienyl)methyl, (3-thienyl)methyl, (2-pyridyl)methyl,1-methyl-1-(2-pyrimidyl)ethyl and the like. The terms “heteroaryloxy”,“heteroaralkoxy”, “heterocycloxy”, “heterocylylalkoxy” denotesheteroaryl, heteroarylalkyl, heterocyclyl, heterocylylalkyl groupsrespectively, as defined above, attached to an oxygen atom.

The term “acyl” used herein, either alone or in combination with otherradicals, denotes a radical containing one to eight carbons such asformyl, acetyl, propanoyl, butanoyl, iso-butanoyl, pentanoyl, hexanoyl,heptanoyl, benzoyl and the like, which may be substituted.

The term “acyloxy” used herein, either alone or in combination withother radicals, denotes a radical acyl, as defined above, directlyattached to an oxygen atom, such as acetyloxy, propionyloxy,butanoyloxy, iso-butanoyloxy, benzoyloxy and the like and may besubstituted.

The term “acylamino” used herein, either alone or in combination withother radicals, denotes an acyl group as defined earlier attached to oneamino group and may be CH₃CONH, C₂H₅CONH, C₃H₇CONH, C₄H₉CONH, C₆H₅CONHand the like, which may be substituted.

The term “mono-substituted amino” used herein, either alone or incombination with other radicals, denotes an amino group, substitutedwith one group selected from (C₁–C₆)alkyl, substituted alkyl, aryl,substituted aryl or arylalkyl groups. Examples of monoalkylamino groupinclude methylamine, ethylamine, n-propylamine, n-butylamine,n-pentylamine and the like and may be substituted.

The term ‘disubstituted amino” used herein, either alone or incombination with other radicals, denotes an amino group, substitutedwith two radicals that may be same or different selected from(C₁–C₆)alkyl, substituted alkyl, aryl, substituted aryl, or arylalkylgroups, such as dimethylamino, methylethylamino, diethylamino,phenylmethyl amino and the like and may be substituted.

The term “arylamino” used herein, either alone or in combination withother radicals, denotes an aryl group, as defined above, linked throughamino having a free valence bond from the nitrogen atom, such asphenylamino, naphthylamino, N-methyl anilino and the like and may besubstituted.

The term “aralkylamino” used herein, either alone or in combination withother radicals, denotes an arylalkyl group as defined above linkedthrough amino having a free valence bond from the nitrogen atom e.g.benzylamino, phenethylamino, 3-phenylpropylamino, 1-napthylmethylamino,2-(1-napthyl)ethylamino and the like and may be substituted.

The term “oxo” or “carbonyl” used herein, either alone (—C═O—) or incombination with other radicals, such as “alkylcarbonyl”, denotes acarbonyl radical (—C═O—) substituted with an alkyl radical such as acylor alkanoyl, as described above.

The term “carboxylic acid” used herein, alone or in combination withother radicals, denotes a —COOH group, and includes derivatives ofcarboxylic acid such as esters and amides. The term “ester” used herein,alone or in combination with other radicals, denotes —COO— group, andincludes carboxylic acid derivatives, where the ester moieties arealkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, and the like,which may be substituted; aryloxycarbonyl group such as phenoxycarbonyl,napthyloxycarbonyl, and the like, which may be substituted;aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl,napthylmethoxycarbonyl, and the like, which may be substituted;heteroaryloxycarbonyl, heteroaralkoxycarbonyl, wherein the heteroarylgroup, is as defined above, which may be substituted;heterocyclyloxycarbonyl, where the heterocyclic group, as definedearlier, which may be substituted.

The term “amide” used herein, alone or in combination with otherradicals, represents an aminocarbonyl radical (H₂N—C═O—), wherein theamino group is mono- or di-substituted or unsubstituted, such asmethylamide, dimethylamide, ethylamide, diethylamide, and the like. Theterm “aminocarbonyl” used herein, either alone or in combination withother radicals, with other terms such as ‘aminocarbonylalkyl”,“n-alkylaminocarbonyl”, “N-arylaminocarbonyl”,“N,N-dialkylaminocarbonyl”, “N-alkyl-N-arylaminocarbonyl”,“N-alkyl-N-hydroxyaminocarbonyl”, and“N-alkyl-N-hydroxyaminocarbonylalkyl”, substituted or unsubstituted. Theterms “N-alkylaminocabonyl” and “N,N-dialkylaminocarbonyl” denotesaminocarbonyl radicals, as defined above, which have been substitutedwith one alkyl radical and with two alkyl radicals, respectively.Preferred are “lower alkylaminocarbonyl” having (C₁–C₆) lower alkylradicals as described above attached to aminocarbonyl radical. The terms“N-arylaminocarbonyl” and “N-alkyl-N-arylaminocarbonyl” denoteamiocarbonyl radicals substituted, respectively with one aryl radical,or one alkyl and one aryl radical. The term “aminocarbonylalkyl”includes alkyl radicals substituted with aminocarbonyl radicals.

The term “hydroxyalkyl” used herein, either alone or in combination withother radicals, denotes an alkyl group, as defined above, substitutedwith one or more hydroxy radicals, such as hydroxymethyl, hydroxyethyl,hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like.

The term “aminoalkyl” used herein, alone or in combination with otherradicals, denotes an amino (—NH₂) moiety attached to an alkyl radical,as defined above, which may be substituted, such as mono- anddi-substituted aminoalkyl. The term “alkylamino” used herein, alone orin combination with other radicals, denotes an alkyl radical, as definedabove, attached to an amino group, which may be substituted, such asmono- and di-substituted alkylamino.

The term “alkoxyalkyl” used herein, alone or in combination with otherradicals, denotes an alkoxy group, as defined above, attached to analkyl group, such as methoxymethyl, ethoxymethyl, methoxyethyl,ethoxyethyl and the like. The term “aryloxyalkyl” used herein, alone orin combination with other radicals, includes phenoxymethyl,napthyloxymethyl, and the like. The term “aralkoxyalkyl” used herein,alone or in combination with other radicals, includes C₆H₅CH₂OCH₂,C₆H₅CH₂OCH₂CH₂, and the like.

The term “(C₁–C₁₂)alkylthio” used herein, either alone or in combinationwith other radicals, denotes a straight or branched or cyclic monovalentsubstituent comprising an alkyl group of one to twelve carbon atoms, asdefined above, linked through a divalent sulfur atom having a freevalence bond from the sulfur atom, such as methylthio, ethylthio,propylthio, butylthio, pentylthio and the like. Examples of cyclicalkylthio are cyclopropylthio, cyclobutylthio, cyclopentylthio,cyclohexylthio and the like, which may be substituted.

The term “thio(C₁–C₁₂)alkyl” used herein, either alone or in combinationwith other radicals, denotes an alkyl group, as defined above, attachedto a group of formula —SR′, where R′ represents hydrogen, alkyl or arylgroup, e.g. thiomethyl, methylthiomethyl, phenylthiomethyl and the like,which may be substituted.

The term “arylthio’ used herein, either alone or in combination withother radicals, denotes an aryl group, as defined above, linked througha divalent sulfur atom, having a free valence bond from the sulfur atomsuch as phenylthio, napthylthio and the like.

The term “(C₁–C₁₂)alkoxycarbonylamino” used herein, alone or incombination with other radicals, denotes an alkoxycarbonyl group, asdefined above, attached to an amino group, such as methoxycarbonylamino,ethoxycarbonylamino, and the like. The term “aryloxycarbonylamino” usedherein, alone or in combination with other radicals, denotes anaryloxycarbonyl group, as defined above, attached to the an amino group,such as C₆H₅OCONH, C₆H₅OCONCH₃, C₆H₅OCONC_(H) ₅, C₆H₄(CH₃O)OCONH,C₆H₄(OCH₃)OCONH, and the like. The term “aralkoxycarbonylamino” usedherein, alone or in combination with other radicals, denotes anaralkoxycarbonyl group, as defined above, attached to an amino groupC₆H₅CH₂OCONH, C₆H₅CH₂CH₂CH₂OCONH, C₆H₅CH₂OCONHCH₃, C₆H₅CH₂OCONC₂H₅,C₆H₄(CH₃)CH₂OCONH, C₆H₄(OCH₃)CH₂OCONH, and the like.

The term “aminocarbonylamino”, “alkylaminocarbonylamino”,“dialkylaminocarbonylamino” used herein, alone or in combination withother radicals, denotes a carbonylamino (—CONH₂) group, attached toamino(NH₂), alkylamino group or dialkylamino group respectively, wherealkyl group is as defined above.

The term “amidino” used herein, either alone or in combination withother radicals, denotes a —C(═NH)—NH₂ radical. The term “alkylamidino”denotes an alkyl radical, as discussed above, attached to an amidinogroup.

The term “guanidino” used herein, either alone or in combination withother radicals, denotes HN═C(NH₂)NH—, suitably substituted with otherradicals, such as alkylguanidino, dialkylguanidino, where the alkylgroup, as defined above is attached to a guanidino group, such asmethylguanidino, ethylguanidino, dimethylguanidino, and the like.

The term “hydrazino” used herein, either alone or in combination withother radicals, denotes —NHNH—, suitably substituted with otherradicals, such as alkyl hydrazino, where an alkyl group, as definedabove is attached to a hydrazino group.

The term “alkoxyamino” used herein, alone or in combination with otherradicals, denotes an alkoxy group, as defined above, attached to anamino group. The term “hydroxyamino” used herein, alone or incombination with other radicals, denotes —NHOH moiety, and may besubstituted.

The term “sulfenyl” or “sulfenyl and its derivatives” used herein, aloneor in combination with other radicals, denotes a bivalent group, —SO— orRSO, where R is substituted or unsubstituted alkyl, aryl, heteroaryl,heterocyclyl, and the like.

The term “sulfonyl” or “sulfones and its derivatives” used herein,either alone or in combination with other radicals, with other termssuch as alkylsulfonyl, denotes divalent radical —SO₂—, or RSO₂—, where Ris substituted or unsubstituted groups selected from alkyl, aryl,heteroaryl, heterocyclyl, and the like. “Alkylsulfonyl” denotes alkylradicals, as defined above, attached to a sulfonyl radical, such asmethylsulfonyl, ethylsulfonyl, propylsulfonyl and the like. The term“arylsulfonyl” used herein, either alone or in combination with otherradicals, denotes aryl radicals, as defined above, attached to asulfonyl radical, such as phenylsulfonyl and the like.

The term “sulfonic acid or its derivatives”, used herein, either aloneor in combination with other radicals, denotes —SO₃H group and itsderivatives such as sulfonylamino(SO₂NH₂); N-alkylalminosulfonyl andN,N-dialkylaminosulfonyl radicals where the sulfonylamino group issubstituted with one and two alkyl groups respectively, such asN-methylaminosulfonyl, N-ethylaminosulfonyl, N,N-dimethylaminosulfonyl,N-methyl-N-ethylaminosulfonyl and the like; N-arylaminosulfonyl andN-alkyl-N-arylaminosulfonyl groups where the sulfonylamino group issubstituted with one aryl radical, or one alkyl and one aryl radical;—SO₃R, wherein ‘R’ represents alkyl, aryl, aralkyl groups, as definedabove, which may be substituted.

The term “phosphonic acid or its derivatives”, used herein, either aloneor in combination with other radicals, denotes P(O)(OH)₂, P(O)(O(C₁–C₆)alkyl)₂, P(O)(O aryl)₂, P(O)(OH)(O(C₁–C₆)alkyl), and the like.

The term “substituted” used in combination with other radicals, denotessuitable substituents on that radical such as substituted alkyl,substituted alkenyl, substituted alkynyl, substituted cycloalkyl,substituted aryl, etc, mentioned anywhere in the specification. Thesuitable substituents include, but are not limited to the followingradicals, alone or in combination with other radicals, such as,hydroxyl, oxo, halo, thio, nitro, amino, cyano, formyl, amidino,guanidino, hydrazino, alkyl, haloalkyl, perhaloalkyl, alkoxy,haloalkoxy, perhaloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,bicycloalkyl, bicycloalkenyl, alkoxy, alkenoxy, cycloalkoxy, aryl,aryloxy, aralkyl, aralkoxy, heterocylyl, heteroaryl, heterocyclylalkyl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, heterocyclyloxy,heterocyclylalkoxy, heterocyclylalkoxyacyl, acyl, acyloxy, acylamino,monosubstituted or disubstituted amino, arylamino, aralkylamino,carboxylic acid and its derivatives such as esters and amides,carbonylamino, hydroxyalkyl, aminoalkyl, alkoxyalkyl, aryloxyalkyl,aralkoxyalkyl, alkylthio, thioalkyl, arylthio, alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkoxyamino, hydroxyl amino, sulfenylderivatives, sulfonyl derivatives, sulfonic acid and its derivatives,phosphonic acid and its derivatives.

The groups R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, and Ar, may besubstituted, where the term “substituted” includes radicals as definedabove, or any other group mentioned in the specification.

Some of the above defined terms may occur more than once in the abovedefined formula (I) and upon such occurences, each such term may bedefined independently of the other.

It is preferred that R⁸ represents (C₁–C₆)alkyl, aralkyl or hydrogen; Zrepresents O or NH or N(C₁–C₃)alkyl; Y represents O atom; X represents Oor S atom; R⁷ represents optionally substituted groups selected fromlinear or branched (C₁–C₆)alkyl, aralkyl or aryl radical; R⁵ and R⁶ eachrepresent a H atom or R⁵ and R⁶ together may represent a bond; Arrepresents a divalent phenyl group or a naphthyl group optionallysubstituted; W represents O or S atom; n represents an integer 2; R¹,R², R³, R⁴ represent hydrogen, formyl, perhaloalkyl, substituted orunsubstituted groups selected from linear or branched (C₁–C₆)alkyl,aralkyl, (C₃–C₆)cycloalkyl, (C₁–C₆)alkoxy, aryl, heterocyclyl,heteroaryl, heterocyclylalkyl, heteroaralkyl, alkoxy, alkylthio,arylthio, acyl, alkoxycarbonyl, aryloxycarbonyl, carboxylic acid and itsderivatives.

It is more preferred that R⁸ represents (C₁–C₃)alkyl, aralkyl orhydrogen; Z represents O atom; Y represents O atom; X represents O atom;R⁷ represents linear or branched (C₁–C₆)alkyl, optionally substitutedwith one or more halogen atoms; R⁵ and R⁶ represent each a hydrogenatom; Ar represents a divalent phenyl group, optionally substituted withhalogen, alkyl, alkoxy groups; W represents O atom; n represents aninteger 2; R², R³ each represent a hydrogen atom and R¹, R⁴ may be sameor different and represent optionally substituted groups selected from(C₁–C₆)alkyl, especially, (C₁–C₄)alkyl such as methyl, ethyl, propyl,iso-propyl, butyl, iso-butyl groups; aralkyl groups such as benzyl,phenethyl; hydroxyalkyl especially hydroxymethyl; aminoalkyl especiallyaminomethyl; aryl, phenyl optionally substituted with one or more groupssuch as halo, nitro, cyano, alkyl, alkenyl, phenyl, alkoxy,1,2-methylenedioxy, heterocyclylalkyl, heteroaralkyl, aryloxy, aralkyl,alkylthio, thioalkyl, hydroxy, alkylcarbonyloxy, halogen, amino,acylamino alkylamino, acyl, alkylsulfinyl, alkylsulfonyl, arylthio,arylsulfenyl, arylsulfonyl, carboxylic acid and its derivatives;heterocyclyl, heteroaryl, acyl, (C₃–C₆)cycloalkyl groups; optionallysubstituted heteroaryl group such as furyl, thienyl, quinolyl,benzofuryl, benzothienyl, pyridyl groups. Alternatively, R¹, R², R³represent hydrogen atom and R⁴ represent optionally substituted groupsselected from aryl, 1,2-methylenedioxyphenyl, heteroaryl, such as furyl,pyridyl, thienyl, benzofuranyl, benzothiophenyl, (C₁–C₄)alkyl,alkylthio, alkoxy, and acyl groups.

Pharmaceutically acceptable salts forming part of this invention areintended to define but not limited to salts of the carboxylic acidmoiety such as alkali metal salts like Li, Na, and K salts; alkalineearth metal salts like Ca and Mg salts; salts of organic bases such aslysine, arginine, guanidine and its derivatives, which may be optionallysubstituted, diethanolamine, choline, tromethamine and the like;ammonium or substituted ammonium salts and aluminium salts. Salts may beacid addition salts which defines but not limited to sulfates,bisulfates, nitrates, phosphates, perchlorates, borates, hydrohalides,acetates, tartrates, maleates, fumarates, maleiates, citrates,succinates, palmoates, methanesulfonates, benzoates, salicylates,hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates,ketoglutarates and the like. Pharmaceutically acceptable solvates may behydrates or comprising other solvents of crystallization such asalcohols.

Particularly useful compounds according to the present inventionincludes

-   (±) Ethyl 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (+) Ethyl 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (−) Ethyl 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (±) Ethyl    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (+) Ethyl    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (−) Ethyl    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (±) Ethyl    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (+) Ethyl    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (−) Ethyl    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (±) Ethyl    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-[4-[2-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl-2-ethoxypropanoate-   (+) Ethyl    3-[4-[2-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl-2-ethoxypropanoate-   (−) Ethyl    3-[4-[2-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl-2-ethoxypropanoate-   (±) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2-ethoxypropanoate-   (+) Ethyl    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2-ethoxypropanoate-   (−) Ethyl    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2-ethoxypropanoate-   (±) Ethyl    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (+) Ethyl    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (−) Ethyl    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate-   (±) Ethyl    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (±) Methyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (+) Methyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (−) Methyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-phenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (±) Propyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (+) Propyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (−) Propyl    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-    [2-(5-methyl-2,3-diphenylpyrro-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate;-   (+) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate;-   (−) Ethyl    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-2-furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-2-furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-2-furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(5-methyl    furan-2-yl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(5-methyl furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(5-methyl furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(2-benzoyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(2-benzoyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(2-benzoyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±) Ethyl 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+) Ethyl 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−) Ethyl 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-3-benzyloxy-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-3-benzyloxy-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-3-benzyloxy-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (±)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (+)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   (−)    Ethyl-3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate;-   Ethyl (E/Z)    3-{4-[2-(5-methyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enenoate;-   Ethyl (Z)    3-{4-[2-(5-methyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enenoate;-   Ethyl (E)    3-{4-[2-(5-methyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enenoate;-   [(2R)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1phenylethyl)propanamide-   [(2S)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)    propanamide-   (±) 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and    its pharmaceutically acceptable salts-   (+) 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and    its pharmaceutically acceptable salts-   (−) 3-{4-[2-(pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and    its pharmaceutically acceptable salts-   (±)    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-{4-[2-(2,5-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-{4-[2-(2,5-diisopropyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-{2-[2-isopropyl-5-(4-methoxyphenyl)pyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-(2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy)phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-(4-(2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy)phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-(2-[2-(4-fluorophenyl)-5-isopropyl-3-phenylpyrrol-1-yl]ethoxy)phenyl)-2-ethoxoypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-(2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy)phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-(4-{2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-{2-[2-(4-fluorophenyl)-5-phenylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-[4-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl]-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-[4-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl]-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-[4-[2-(2-phenyl-3-carboxy-5-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl]-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salt thereof-   (+)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-(4-{3-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]propoxy}phenyl)-2ethoxypropanoic    acid and its pharmaceutically acceptable salts.-   (±)    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (+)    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (−)    3-{4-[2-(2-isopropyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts-   (±)    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(2,4-dimethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2-ethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2-acetylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-propylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-n-butylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-    {4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-propoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-    ethoxypropanoic acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-3-phenylpyrrol-1-yl)ethoxy]phenyl}-2-    ethoxypropanoic acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(3-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(2-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-methoxyphenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-bromophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-fluorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-chlorophenyl)pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(4-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2,3-diphenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(2,5-diisopropylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-isopropyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-(4-{2-[2-(4-fluorophenyl)-5-isopropyl-4-phenylcarbamoylpyrrol-1-yl]ethoxy}phenyl)-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(2-methylthiopyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2,5-diethylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    33-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;.-   (−) 3-{4-[2-(5-ethyl-2-(2-phenylethyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(3-methoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-cyclohexyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-biphenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(5-methyl-furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(5-methyl-furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(5-methyl-furan-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-thiomethyl phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-cyanophenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-phenoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-1′-(toluene-4-sulfonyl)-1′H-[2,2′]bipyrrolyl-1-yl])ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(3,4-dimethoxyphenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-methanesulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-acetylamino-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-(2-piperidin-1-yl-ethoxy)-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-vinyloxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-phenylsulfanyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2 (4-phenylsulfinyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-methanesulfonyl-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(4-cyclohexylmethoxy-phenyl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2-benzoyl pyrrol-1-yl)ethoxy]phenyl }-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-cyclopropyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(benzofuran-2-yl)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(3-carboxymethyl-2-methyl-5-phenyl    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±) 3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (+) 3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (−) 3-{4-[2-(5-methyl-2-(Benzo[1,3]dioxol-5-yl-)    pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic acid and its    pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(naphthalen-1-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(3-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(5-bromo-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-isopropoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(3,5-dimethyl-2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    aid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-benzyloxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-hydroxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts,-   (±) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−) 3-{4-[2-(2-phenyl-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(5-chloro-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(4-ethoxy-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(5-methyl-thiophen-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(2,3-dimethyl-5-phenyl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(quinolin-2-yl-)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(pyridin-4-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(pyridin-2-yl)-pyrrol-1-yl)ethoxy]phenyl)}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (±)    3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (+)    3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (−)    3-{4-[2-(5-methyl-2-(pyridin-3-yl)-pyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoic    acid and its pharmaceutically acceptable salts;-   (E/Z)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic    acid and its pharmaceutically acceptable salts;-   (E)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic    acid and its pharmaceutically acceptable salts; and-   (Z)    3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxyprop-2-enoic    acid and its pharmaceutically acceptable salts.

The signs (+) and (−) in the beginning of the name or number of acompound intends to denote the dextrorotatory or laevorotatory isomersof the compound. They may contain only one optical isomer or varyingamounts of the other optical isomer, keeping the net sign of rotation ofplane polarised light (+) or (−) as the case may be. The sign (±) in thebeginning of the name or number of a compound intends to indicate aracemic mixture of the two enantiomers with almost zero net rotation ofthe plane polarized light. The present invention encompasses the use ofnot only the compounds of present invention described in formula (I) butalso the metabolic products of these compounds formed in vivo for thetreatment of diseases mentioned anywhere in the specificaiton.

The present invention also provides methods for the preparation of novelcompounds described in the general formula (I), their tautomeric forms,their derivatives, their analogs, their stereoisomers, theirpharmaceutically acceptable salts and their pharmaceutically acceptablesolvates, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, W, X, Y, Z, Ar and nare as defined- earlier. These methods are described below, comprising:

The reaction of a compound of general formula (1a), wherein all symbolsare as defined earlier with a compound of formula (1b) which may beoptically active or racemic, wherein all symbols are as defined earlierto yield a compound of general formula (I) may be carried out usingPaal-Knorr cyclization (Paal C. Ber., 1885, 18, 367; Knorr, L., Ber.,1885, 18, 299). The reaction may be carried out neat or in the presenceof a solvent or a mixture thereof such as tetrahydrofuran,hexane,cyclohexane, toluene, methanol, ethanol, heptane, petroleumether, xylene, benzene, ethyl acetate, tert-butyl acetate,1,2-dichloroethane, iso-propanol, dioxane, cyclohexane, acetonitrile andthe like. The reaction temperature may range from 0° C. to the refluxtemperature of the solvent(s) used. The water produced may be removed byusing a Dean Stark water separator or by water scavengers such asmolecular sieves. The reaction may be carried out in the absence orpresence of an inert atmosphere such as N₂, He or Ar. The reaction maybe carried out under acidic condition provided by acids like aceticacid, propanoic acid, butyric acid, isobutyric acid, pivalic acid,p-toluenesulfonic acid, camphorsulfonic acid, benzenesulfonic acid,trifluoroacetic acid, chloroacetic acid, chloropropanoic acid,phenylacetic acid, phenylpropanoic acid, malonic acid, succinic acid,benzoic acid, halogenated benzoic acid, toluic acid and the like.Mineral acids such as HCl or HBr may also be used. The reaction time mayrange from 5 minutes to 72 hours, preferably from 1 to 48 hours.

The reaction of compound of formula (1c), where all symbols are asdefined earlier and L¹ represents a leaving group such as halogen atom,p-toluenesulfonate, methanesulfonate, trifluoromethanesulfonate and thelike with a compound of formula (1d) which may be optically active orracemic, where W is either O or S and all other symbols are as definedearlier, to produce a compound of general formula (I). This reaction maybe carried out in the presence of solvents such as acetone,tetrahydrofuran, dimethylsulfoxide, dioxane, acetonitrile, dimethylformamide, DME, benzene, toluene, pet, ether, heptane, hexane,2-butanone, xylene, alcohols such as methanol, ethanol, propanol,butanol, iso-butanol, tert-butanol, pentanol and the like or a mixturethereof. Base such as alkali metal carbonate such as K₂CO₃, Na₂CO₃,CsCO₃, and the like; or alkali metal hydroxide such as NaOH, KOH and thelike, may be used during this reaction. Alkali metal hydrides such asNaH, KH can be used whenever solvent employed is not protic or containcarbonyl group. The reaction may be carried out at a temperature in therange 0° C. to reflux temperature of the solvent(s) used and thereaction time may range from 1 to 48 hours.

The reaction of compound of general formula (1e) where all symbols areas defined earlier and W represents oxygen atom, with a compound ofgeneral formula (1d) which may be optically active or racemic, where Wis O or S and all other symbols are as defined earlier may be carriedout using coupling agents such as DCC, EDC, triaryl phosphine/dialkylazadicarboxylate such as PPh₃/DEAD or PPh₃/DIAD and the like. Inertatmosphere may be maintained using N₂, Ar or He. Solvents such astetrahydrofuran, dioxane, DME, toluene, dichloromethane, chloroform,carbon tetrachloride, acetonitrile and the like may be used. Compoundssuch as 4-dimethylaminopyridine, hydroxybenzotriazole etc. may be usedin the range of 0.05 to 2 equivalents. The reaction temperature in therange of 0° C. to reflux temperature of the solvent may be used,preferably, 20° C. to 80° C. The duration of the reaction may range from0.5 to 24 h, preferably 0.5 to 12 hours.

The reaction of a compound of general formula (1h) wherein all thesymbols are as defined earlier, with a compound of formula (1i), whereall the symbols are as defined earlier and R represents (C₁–C₈) alkyl toafford a compound of formula (I) where R⁵ and R⁶ represent a bond andall other symbols are as defined earlier, may be carried out underWittig Homer reaction conditions in the presence of a base such asalkali metal hydrides, like NaH or KH, alkali metal alkoxides such asNaOMe, NaOEt, K⁺ t-BuO⁻ or mixture thereof, organolithiums like CH₃Li,BuLi, sec-BuLi, LDA and the like. Aprotic solvents such as THF, dioxane,DMF, DMSO, DME and the like or mixture thereof may be employed. HMPAfavours the progression of the reaction but not essential. The reactionmay be carried out at a temperature ranging from −80° C. to 100° C.,preferably from 0° C. to 30° C. The reaction proceeds more effectivelyunder anhydrous and inert conditions.

The compound of formula (I) where R⁵ and R⁶ represent a bond may bereduced to a compound of general formula (I) where R⁵ and R⁶ eachrepresent hydrogen atom by reacting with hydrogen gas in the presence ofa catalyst such as 5–10% Pd/C, Rh/C, Pt/C Raney Ni and the like, 5–100%w/w of the catalyst may be employed or the mixture thereof. The pressureof hydrogen gas may be one atmosphere to 80 psi. Suitable solvents arealcohols such as ethanol, methanol and the like, ethyl acetate, THF,dioxane, acetic acid and the like. Temperature may be in the range of20° C. to 80° C., may be used for this reduction process. Metal-solventsuch as magnesium in alcohol or sodium amalgam in alcohol may also beused, for this reduction process.

According to a feature of the present invention, there is provided anintermediate of formula (1h),

wherein R¹, R², R³, R⁴ may be same or different, and represent hydrogen,halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, hydroxy,thio, amino, nitro, cyano, formyl, amidino, guanidino, or substituted orunsubstituted groups selected from linear or branched (C₁–C₁₂)alkyl,linear or branched (C₁–C₁₂)alkenyl, linear or branched (C₁–C₁₂)alkynyl,(C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl, bicycloalkyl, bicycloalkenyl,(C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy, cyclo(C₃–C₇)alkoxy, aryl, aryloxy,aralkyl, ar(C₁–C₁₂)alkoxy, heterocyclyl, heteroaryl,heterocyclyl(C₁–C₁₂)alkyl, heteroar(C₁–C₁₂)alkyl, heteroaryloxy,heteroar(C₁–C₁₂)alkoxy, heterocycloxy, heterocyclylalkyloxy, acyl,acyloxy, acylamino, mono-substituted or di-substituted amino, arylamino,aralkylamino, carboxylic acid and its derivatives such as esters andamides, hydroxyalkyl, aminoalkyl, mono-substituted or di-substitutedaminoalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁–C₁₂)alkylthio,thio(C₁–C₁₂)alkyl, arylthio, (C₁–C₁₂)alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, alkyl hydrazino, alkoxyamino, hydroxyl amino, derivatives ofsulfenyl and sulfonyl groups, sulfonic acid and its derivatives,phosphonic acid and its derivatives; n represents an integer varyingfrom 1 to 8; W represents O, S or NR⁹, where R⁹ represents hydrogen,(C₁–C₁₂)alkyl or aryl groups; Ar represents a substituted orunsubstituted divalent single or fused aromatic, heteroaromatic or aheterocyclic group;

According to another feature of the present invention, there is provideda process for the preparation of intermediate of the general formula(1h) as defined earlier which comprises reacting a compound of generalformula (1c),

wherein, R¹–R⁴, n are as defined earlier and L¹ is a halogen atom suchas chlorine, bromine or iodine or a leaving group such asmethanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate and thelike with the compound of the formula (1j), where Ar and W are asdefined earlier.

The reaction of the compound of formula (1c) with the compound offormula (1j) to produce a compound of formula (1h) may be carried out inthe presence of solvents such as acetone, THF, DMSO, dioxane,2-butanone, acetonitrile, DMF, DME, benzene, toluene, xylene, alcoholssuch as methanol, ethanol, propanol, butanol, iso-butanol, tert-butanol,pentanol and the like or a mixture thereof. Bases such as alkali metalcarbonates such as K₂CO₃, Na₂CO₃, CsCO₃ and the like may be used; alkalimetal hydroxides like NaOH, KOH and the like; or mixtures thereof may beused. Alkali metal hydrides such as NaH, KH and the like, may be used incases when the solvent used is not protic and does not contain carbonylgroup. The reaction temperature may range from 20° C. to refluxtemperature of the solvent(s) used and the reaction time may range from1 to 48 hours. The inert atmosphere may be maintained by using inertgases such as N₂, Ar or He.

Alternatively, the intermediate of the general formula (1h), can also beprepared by the reaction of compound of general formula (1e),

wherein R¹–R⁴, n and W are as defined earlier and with a compound of theformula (1k), where Ar is as defined earlier and L² is a halogen atomsuch as fluorine, chlorine, bromine or iodine. The reaction of thecompound of formula (1e) with the compound of formula (1k) to produce acompound of formula (1h) may be carried out in the presence of solventssuch as THF, DMF, DMSO, DME and the like. Mixture of solvents may beused. The inert atmosphere may be maintained by using inert gases suchas N₂, Ar or He. The reaction may be effected in the presence of a basesuch as K₂CO₃, Na₂CO₃, NaH or mixtures thereof. The reaction temperaturemay range from 20° C. to 150° C., preferably at a temperature in therange from 30° C. to 100° C. The duration of reaction may range from 1to 24 hours, preferably from 2 to 6 hours.

The reaction of compound of general formula (1e) wherein W represents Oand all other symbols are as defined earlier with the compound offormula (1j) may be carried out using suitable coupling agents such asdicyclohexyl urea, triarylphosphine/dialkylazadicarboxylate such asPPh₃/DEAD and the like. The reaction may be carried out in the presenceof solvents such as THF, DME, CH₂Cl₂, CHCl₃ toluene, acetonitrile,carbontetrachloride and the like. The inert atmosphere may be maintainedby using inert gases such as N₂, Ar or He. The reaction may be effectedin the presence of DMAP, HOBT and they must be used in the range of 0.05to 2 equivalents, preferably 0.25 to 1 equivalents. The reactiontemperature may range from 0° C. to 100° C., preferably at a temperaturein the range from 20° C. to 80° C. the duration of reaction of thereaction may range from 0.5 to 24 hours, preferably from 6 to 12 hours.

In another embodiment of this invention, there is provided a process forthe preparation of a compound of the general formula (1c), whichcomprises reacting the compound of general formula (1a) wherein R¹–R⁴are as defined earlier,

with either substituted amino compound (1m), where all symbols are is asdefined earlier, to yield the intermediate of the general formula (1c).

In yet another embodiment of this invention, there is provided a processfor the preparation of a compound of the general formula (1e), whichcomprises reacting the compound of general formula (1a) wherein R¹–R⁴are as defined earlier,

with either substituted amino compound (1l), where all symbols are is asdefined earlier, to yield the intermediate of the general formula (1e).

The reactions of a compound of general formula (1a) with a compound ofgeneral formula, (1l) or a compound of general formula (1m) may becarried out neat or in presence of solvents or a mixture thereof such astetrahydrofuran, hexane, toluene, methanol, ethanol, heptane, petroleumether, xylene, benzene, ethyl acetate, tert-butyl acetate,1,2-dichloroethane, iso-propanol, tert-butanol, dioxane, cyclohexane,acetonitrile and the like. The reaction temperature may range from 0° C.to the reflux temperature of the solvent(s) used. The water produced maybe removed by using a Dean Stark water separator or by water scavengerssuch as molecular sieves. The reaction may be carried out in thepresence of an inert atmosphere such as N₂, He or Ar. The reaction maybe carried out in the presence of an acid, such as acetic acid,propanoic acid, butyric acid, isobutyric acid, pivalic acid,p-toluenesulfonic acid, camphorsulfonic acid, benzenesulfonic acid,trifluoroacetic acid, chloroacetic acid, chloropropanoic acid,phenylacetic acid, phenylpropanoic acid, malonic acid, succinic acid,benzoic acid, halogenated benzoic acid, toluic acid and the like.

Yet another embodiment of this invention, there is provided an alternateprocess for the preparation of a compound of the general formula (1c),which comprises reacting the compound of general formula (1n) whereinR¹–R⁴ are as defined earlier,

with the compound of formula (1o) where L¹ and L₂ may be same ordifferent and represent leaving groups such as halogen atom as Cl, Br,or I, methanesulfonate, p-toluenesulfonate and the like; and n asdefined earlier.

In yet another embodiment of this invention, there is provided analternate process for the preparation of a compound of the generalformula (1e), which comprises reacting the compound of general formula(1n) where R¹–R⁴ are as defined earlier,

with the compound of formula (1p) where L₂ represent leaving groups suchas halogen atom as Cl, Br, or I, methanesulfonate, p-toluenesulfonateand the like; and n as defined earlier.

The reaction of compound of general formula (1n), with either (1o) or(1p) may be carried out in solvents such as alcohol like methanol,ethanol, iso-propanol and the like; THF, dioxane, DMSO, DMF,acetonitrile, heptane, benzene, toluene, xylene and the like. Thereaction may be carried out in presence of bases such as NaH, KH,Na₂CO₃, K₂CO₃, NaOH, KOH, LiNH₂, NaNH₂ and the like. Phase transfercatalyst such as tetrabutyl ammonium halide, tetrabutyl ammoniumhydroxide (TBAH) and the like may be used. The reaction temperature mayrange from 0° C. to the reflux temperature of the solvent employed. Thereaction may be carried out in the presence of an inert atmosphere suchas N₂, He or Ar.

In another embodiment of this invention, there is provided a process forthe preparation of a compound of the general formula (1e), wherein R¹–R⁴and n are as defined earlier and W represents O, which comprisesreducing the corresponding acid

The reduction of compound of general formula (1q) may be carried out inpresence of solvents or a mixture thereof such as tetrahydrofuran,dioxane, ether and the like. The reaction temperature may range from 0°C. to the reflux temperature of the solvent(s) used. The reaction may becarried out in the presence of an inert atmosphere such as N₂, He or Ar.Suitable reducing agent such as sodium borohydride/iodine, diborane andits derivative, LiAlH₄ and the like may be used.

The compound of general formula (1q) may be prepared by the reaction ofcompound of general formula (1n) with a compound of L₁(CH₂)_(n−1)COOR,where L₁ and R are as defined earlier, followed by hydrolysis of theester group to acid using methods commonly used.

The compounds of the present invention have asymmetric centers and occureither as racemates or racemic mixtures as well as individualdiastereomers of any of the possible isomers, including optical isomers,being included in the present invention The stereoisomers of thecompounds of the present invention may be prepared by one or more wayspresented below:

-   -   i. One or more of the reagents may be used in their single        isomeric form. For example, compound (1b) or (1d) may be pure        stereoisomers.    -   ii. Optically pure catalysts or chiral ligands along with metal        catalysts may be employed in the reduction process. The metal        catalyst may be Rhodium, Ruthenium, Indium and the like. The        chiral ligands may preferably be chiral phosphines. (Principles        of Asymmetric synthesis J E Baldwin Ed. Tetrahedron series,        Volume 14, Page no. 311–316)    -   iii. Mixture of stereoisomers may be resolved by conventional        methods such as microbial resolution, resolving the        diastereomeric salts formed with chiral acids or chiral bases.        Chiral acids may be tartaric acid, mandelic acid, lactic acid,        camphorsulfonic acid, amino acids and the like. Chiral bases may        be cinchona alkaloids, (+) or (−) brucine, α-methyl benzylamine,        (+) or (−) phenyl glycinol, ephedrine, amino sugars such as        glucosamines or a basic amino acid such as lysine, arginine and        the like.    -   iv. Resolution of the mixture of stereoisomers may also be        effected by chemical methods by derivatization of the compound        with a chiral compound such as chiral amines, chiral acids,        chiral amino alcohols, amino acids into a 1:1 mixture of        diastereomers and the diastereomers may be separated by        conventional methods of fractional crystallization,        chromatography and the like followed by cleaving the derivative        (Jaques et al. “Enantiomers, Racemates and Resolution”, Wiley        Interscience, 1981; R. A. Sheldon, in “Chirotechnology”, Marcel        Dekker, Inc. NY, Basel, 1993, 173–204 and references        therein; A. N. Collins, G. N. Sheldrack and J Crosby, in        “Chirality in Industry II”, John Wiley & Sons, Inc, 1997, 81–98        and references therein; E. L. Eliel and S. H. Wilen, in        “Stereochemistry of Organic Compound”, John Wiley & Sons, Inc,        1999, 297–464 and references therein.)

It will be appreciated that in any of the above mentioned reactions anyreactive group in the substrate molecule may be protected, according toconventional chemical practice. Suitable protecting groups in any of theabove mentioned reactions are those used conventionally in the art. Themethods of formation and removal in such protecting groups are thoseconventional methods appropriate to the molecule being protected. T. W.Greene and P. G. M. Wuts “Protective groups in Organic Synthesis”, JohnWiley & Sons, Inc, 1999, 3^(rd) Ed., 201–245 along with referencestherein.

It will be appreciated that the above-mentioned preparation of thecompounds of Formula (I), or a pharmaceutically acceptable salt thereof,and/or pharmaceutically acceptable solvate thereof is a stereoselectiveprocedure and that the compound of formula (I) is a single stereoisomer.Favorably, a compound of formula (I) is present in admixture with lessthan 50% w/w of its racemic isomer, suitably 80–100% and preferably90–100% pure, such as 90–95%, most preferably 95–100%, for example 95%,96%, 97%, 98%, 99% and 99.99% optically pure.

Preferably the compounds of Formula (I), or a pharmaceuticallyacceptable salt thereof, and/or pharmaceutically acceptable solvatethereof is in optically pure form.

The absolute stereochemistry of the compounds may be determined usingconventional methods, such as X-ray crystallography.

The pharmaceutically acceptable salts forming a part of this inventionmay be prepared by treating the compound of formula (I) with 1–6equivalents of a base such as sodium hydride, sodium methoxide, sodiumethoxide, sodium hydroxide, potassium tert-butoxide, calcium hydroxide,calcium acetate, calcium chloride, magnesium hydroxide, magnesiumchloride, magnesium alkoxide and the like. Solvents such as water,acetone, ether, THF, methanol, ethanol, t-butanol, 2-butanone, dioxane,propanol, butanol, isopropanol, diisopropyl ether, tert-butyl ether ormixtures thereof may be used. Organic bases such as lysine, arginine,methyl benzylamine, ethanolamine, diethanolamine, tromethamine, choline,guanidine and their derivatives may be used. Acid addition salts,wherever applicable may be prepared by treatment with acids such astartaric acid, mandelic acid, fumaric acid, malic acid, lactic acid,maleic acid, salicylic acid, citric acid, ascorbic acid, benzenesulfonic acid, p-toluene sulfonic acid, hydroxynaphthoic acid, methanesulfonic acid, acetic acid, benzoic acid, succinic acid, palmitic acid,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and thelike in solvents such as water, alcohols, ethers, ethyl acetate,dioxane, THF, acetonitrile, DMF or a lower alkyl ketone such as acetone,or mixtures thereof.

Another aspect of the present invention comprises a pharmaceuticalcomposition, containing at least one of the compounds of the generalformula (I), their derivatives, their analogs, their tautomeric forms,their stereoisomers, their pharmaceutically acceptable salts, theirpharmaceutically acceptable solvates thereof as an active ingredient,together with pharmaceutically employed carriers diluents and the like.

Pharmaceutical compositions containing a compound of the presentinvention may be prepared by conventional techniques, e.g. as describedin Remington: the Science and Practice of Pharmacy, 19^(th) Ed., 1995.The compositions may be in the conventional forms, such as capsules,tablets, powders, solutions, suspensions, syrups, aerosols or topicalapplications. They may contain suitable solid or liquid carriers or insuitable sterile media to form injectable solutions or suspensions. Thecompositions may contain 0.5 to 20%, preferably 0.5 to 10% by weight ofthe active compound, the remaining being pharmaceutically acceptablecarriers, excipients, diluents, solvents and the like.

Typical compositions containing a compound of formula (I) or apharmaceutically acceptable acid addition salt thereof, associated witha pharmaceutically acceptable excipients which may be a carrier or adiluent or be diluted by a carrier, or enclosed within a carrier whichcan be in the form of a capsule, sachet, paper or other container. Whenthe carrier serves as a diluent, it may be a solid, semi-solid, orliquid material, which acts as a vehicle, excipients or medium for theactive compound. The active compound can be absorbed on a granular solidcontainer for example in a sachet. Some of suitable carriers are water,salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylatedcastor oil, peanut oil, olive oil, gelatin, lactose, terra alba,sucrose, cyclodextrin, amylose, magnesium sterate, talc, gelatin, agar,pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicicacid, fatty acids, fatty acid amines, fatty acids monoglycerides anddiglycerides, pentaerythritol fatty acids esters, polyoxyethylene,hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrieror diluent may include any sustained release material known in the art,such as glyceryl monostearate or glyceryl distearate, alone or mixedwith a wax. The formulations may also include wetting agents,emulsifying and suspending agents, preservatives, sweetening agents orflavoring agents. The formulations of the invention may be formulated soas to provide quick, sustained, or delayed release of the activeingredient after administration to the patient by employing procedureswell known in the art.

The pharmaceutical compositions can be sterilized and mixed, if desired,with auxiliary agents, emulsifiers, buffers and/or coloring substancesand the like, which do not deleteriously react with the activecompounds.

The route of administration may be any route, which effectivelytransports the active drug to the appropriate or desired site of actioneffectively, such as oral, nasal, transdermal, pulmonary or parentale.g. rectal, depot, subcutaneous, intravenous, intraurethral,intramuscular, intranasal, ophthalmic solution or an ointment,preferably through oral route.

If a solid carrier is used for oral administration, the preparation maybe tabletted, placed in a hard gelatin capsule in powder or pellet formor it can be in the form of a troche or lozenge. If a liquid carrier isused, the preparation may be in the form of a syrup, emulsion, softgelatin capsule or sterile injectable liquid such as an aqueous ornon-aqueous liquid suspension or solution.

For nasal administration, the preparation may contain a compound offormula (I) dissolved or suspended in a liquid carrier, in particular anaqueous carrier, for aerosol application. The carrier may containadditives such as solubilizing agent, e.g. propylene glycol,surfactants, absorption enhancers such as lecithin (phosphatidylcholine)or cyclodextrin, or preservatives such as parabens.

For parental application, particularly suitable are injectable solutionsor suspensions, preferably aqueous solutions with the active compounddissolved in polyhydroxylated castor oil.

Tablet, dragees or capsules having talc and/or a carbohydrate carrier orbinder or the like are particularly suitable for oral application.Preferably, carriers for tablets, dragees or capsules include lactose,corn starch and/or potato starch. A syrup or elixir can be used in caseswhere a sweetened vehicle can be employed.

A typical tablet which may be prepared by conventional tablettingtechniques may contain:

Active compound (as free compound or salt thereof) 5.0 mg Colloidalsilicon dioxide 1.5 mg Cellulose, microcrytalline 70.0 mg  Modifiedcellulose gum 7.5 mg Magnesium sterate ad. Coating: HPMC approx 9.0 mg*Mywacett 9–40 T approx. 0.9 mg *Acylated monoglyceride used asplasticizer for film coating.

The compounds of general formula (I) or the compositions thereof areuseful for the treatment and/or prophylaxis of disease caused bymetabolic disorders such as hyperlipidemia, insulin resistance, Leptinresistance, hyperglycemia, obesity, or inflammation.

These compounds are useful for the treatment of hypercholesteremia,familial hypercholesteremia, hypertriglyceridemia, type 2 diabetes,dyslipidemia, disorders related to syndrome X such as hypertension,obesity, insulin resistance, coronary heart disease, atherosclerosis,xanthoma, stroke, peripheral vascular diseases and related disorders,diabetic complications, certain renal diseases such asglomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensivenephrosclerosis, retinopathy, nephropathy, psoriasis, polycystic ovariansyndrome, osteoporosis, inflammatory bowel diseases, myotonic dystrophy,arteriosclerosis, Xanthoma, pancreatitis and for the treatment ofcancer.

The compounds of the invention may be administered to a mammal,especially, a human in need of such treatment, prevention, elimination,alleviation or amelioration of diseases mentioned above.

The compounds of the present invention are effective over a wide dosagerange, however, the exact dosage, mode of administration and form ofcomposition depends upon the subject to be treated and is determined bythe physician or veterinarian responsible for treating the subject.Generally, dosages from about 0.025 to about 200 mg preferably fromabout 0.1 to about 100 mg, per day may be used. Generally, the unitdosage form comprises about 0.01 to 100 mg of the compound of formula(I), as an active ingredient together with a pharmaceutically acceptablecarrier. Usually suitable dosage forms for nasal, oral, transdermal orpulmonary administration comprises from about 0.001 mg to about 100 mg,preferably from 0.01 mg to about 50 mg of the active ingredient mixedwith a pharmaceutically acceptable carrier or diluent.

In another aspect of the present invention, method of treatment and/orprevention of the diseases mentioned above are provided.

In a further aspect of the present invention, use of one or morecompounds of the general formula (I) or pharmaceutically acceptablesalts, for the preparation of a medicament thereof for the treatmentand/or prevention of diseases mentioned in this document is provided.

In still further aspect of the present invention use of the compounds ofthe present invention alone or in combination with statins, glitazones,biguanides, angiotensin II inhibitors, aspirin, insulin secretagogue,β-sitosterol inhibitor, sulfonylureas, insulin, fibric acid derivatives,nicotinic acid, cholestyramine, cholestipol or probucol, α-glycosidaseinhibitors or antioxidants, which may be administered together or withinsuch a period as to act synergistically together.

The invention is explained in detail by the examples given below, whichare provided by way of illustration only and therefore should not beconstrued to limit the scope of the invention.

(1H NMR spectral data given in the tables (vide infra) are recordedusing a 300 MHz spectrometer (Bruker AVANCE-300) and reported in δscale. Until and otherwise mentioned, the solvent used for NMR is CDCl₃using Tetramethyl silane as the internal standard.)

PREPARATION 1 Preparation of1-(2-hydroxyethyl)-5-ethyl-2phenyl-1H-pyrrole (Compound No. 17)

A mixture of 1-phenyl-hexane-1,4-dione (5 g), ethanol amine (1.6 g) andpivalic acid (2.15 g) in a solvent mixture containingn-heptane:tetrahydrofuran:toluene (4:1:1, 50 mL) was refluxed withstirring at 110–120° C. Water formed during the reaction was removedazeotropically during 3 to 4 hrs. The reaction mixture was cooled andthe solvent was removed. The residue obtained was dissolved indichloromethane (50 mL), washed with saturated sodium bicarbonatesolution (50 mL), water (50 mL), and then with brine (50 mL), dried(Na₂SO₄) and the solvent was evaporated. The crude compound obtained asan oily mass. The crude substance was used in the next step withoutpurification.

In the like manner to that described in Preparation 1, the followingcompounds of general formula (1e) were prepared from the appropriatelysubstituted diketones as mentioned in Table 1. The latter can besynthesized by using various routes found in literature.

TABLE 1 (1e)

Comp. Substituents on the pyrrole ring in (1e) No. R¹ R² R³ R⁴ 1. CH₃ HH CH₂CH₃ Mol. Wt. = 153 Yield = 53% ¹H: 1.26(3H, t, J=7.4 Hz); 2.22(3H,s); 2.56(2H, q, J=7.4 Hz); 3.71(2H, t, J=5.86 Hz); 3.88(2H, t, J=5.89Hz); 5.79–5.81(2H, m). 2. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 167 Yield = 36%¹H: 1.02(3H, t, J=7 Hz); 1.65(2H, m); 2.25(3H, s); 2.5(2H, t, J=7.7 Hz);4.1(2H, t, J=5.9 Hz); 4.35(2H, t, J=5.9 Hz); 5.8–5.82(2H, m). 3. CH₃ H H(CH₂)₃CH₃ Mol. Wt. = 181 Yield = 58% ¹H: 0.94(3H, t, J=7.2 Hz);1.36–1.4(2H, m); 1.58–1.67(2H, m); 2.22(3H, s); 2.53(2H, t, J=7.7 Hz);3.7(2H, t, J=5.8 Hz); 3.89(2H, t, J=5.8 Hz); 5.7–5.8(2H, m). 4. CH₃ H H

Mol. Wt. = 201 Yield = 62% ¹H: 2.33(3H, s); 3.5–3.6(2H, t, J=5.9 Hz);4.05–4.09(2H, t, J=6.0 Hz); 5.95(1H, d, J=3.3 Hz); 6.09(1H, d, J=3.3Hz); 7.25–7.29(1H, m); 7.30–7.38(4H, m). 5. CH₃ H H

Mol. Wt. = 215 Yield = 55% ¹H: 2.32(3H, s); 2.37(3H, s); 3.59(2H, t,J=6.9 Hz); 4.10(2H, t, J=6.9 Hz); 5.94(1H, d, J=3.36 Hz); 6.0(1H, d,J=3.36 Hz); 7.2(2H, d, J=8.5 Hz); 7.25(2H, d, J=8.5 Hz) 6. CH₃ H H

Mol. Wt. = 215 Yield = 60% ¹H: 2.32(3H, s); 2.36(3H, s); 3.57(2H, t, J=6Hz); 4.08(2H, t, J=6.06 Hz); 5.94(1H, d, J=2.28 Hz); 6.1(1H, d, J=3.39Hz); 7.09–7.3(4H, m). 7. CH₃ H H

Mol. Wt. = 215 Yield = 60% ¹H: 2.32(3H, s); 2.36(3H, s); 3.58(2H, t, J=6Hz); 4.07(2H, t, J=6.06 Hz); 5.94(1H, d, J=2.28 Hz); 6.07(1H, d, J=3.39Hz); 7.09–7.15(2H, m); 7.24–7.29(2H, m). 8. CH₃ H H

Mol. Wt. = 231 Yield = 45% ¹H: 2.3(3H, s); 3.53(2H, t, J=6.9 Hz);3.84(3H, s); 4.0(2H, t, J=6.9 Hz); 5.9(1H, d, J=3.36 Hz); 6.0(1H, d,J=3.36 Hz); 6.95(2H, d, J=6.78 Hz); 7.2(2H, d, J=6.78 Hz). 9. CH₃ H H

Mol. Wt. = 280 Yield = 55% ¹H: 2.32(3H, s); 3.61–3.63(2H, m) 4.05(2H, t,J = 6.2 Hz); 5.95(1H, dd); 6.1(1H, d, J=3.4 Hz); 7.25–7.3(2H, m);7.47–7.52(2H, m). 10. CH₃ H H

Mol. Wt. = 219 Yield = 32% ¹H: 2.3(3H, s); 3.6(2H, t, J=6.0 Hz);4.05(2H, t, J=6.0 Hz); 5.9(1H, d, J=2.8); 6.0(1H, d, J=3.3 Hz);7.04–7.1(2H, m); 7.26–7.37(2H, m) 11. CH₃ H H

Mol. Wt. = 235.5 Yield = 61% ¹H: 2.3(3H, s); 3.6(2H, t, J=5.9 Hz);4.12(2H, t, J=5.9 Hz); 5.97(1H, d, J=3.2 Hz); 6.10(1H, d, J=3.2 Hz);7.09–7.37(4H, m). 12. CH₃ H

Mol. Wt. = 277 Yield = 90% ¹H: 2.37(3H, s); 3.5(2H, t, J=6 Hz); 3.95(2H,t, J=6.0 Hz); 6.2(1H, d, J=2.8); 7.1–7.4(10H, m). 13. i-Pr H H i-Pr Mol.Wt. = 195 Yield = 93% ¹H: 1.21–1.24(12H, d, J=6.7 Hz); 2.91–2.98(2H, m);3.77(2H, t, J=6.2 Hz); 4.01(2H, t, J=6.2 Hz); 5.8(2H, s). 14. i-Pr H H

Mol. Wt. = 229 Yield = 86% ¹H: 1.29(6H, d, J=6.78 Hz); 3.0–3.05(1H, m);3.51(2H, t, J=6.21 Hz); 4.12(2H, t, J =6.25 Hz); 6.0(1H, d, J=3.54 Hz);6.125(1H, d, J=3.54 Hz); 7.27–7.31(3H, m) 7.37(2H, m) 15. i-Pr

H

Mol. Wt. = 366 Yield = 45% ¹H: 1.43–1.45(6H, d, J=7.2 Hz); 3.3–3.4(1H,m); 4.09–4.1(2H, m); 3.80–3.85(2H, m); 6.85(1H, s); 7.0–7.5(9H, m). 16.—C₂H₅ H H —C₂H₅ Mol. Wt. = 167 Yield = 82% ¹H: 1.26(6H, t, J=7.4 Hz);2.59(4H, q, J=7.4 Hz); 3.76(2H, t, J=5.8 Hz); 3.93(2H, t, J=5.9 Hz);5.86(2H, s) 17. —C₂H₅ H H

Mol. Wt. = 215 Yield = 82% ¹H: 1.32(3H, t, J=7.3 Hz); 2.68(2H, q, J=7.6Hz); 3.57(2H, t, J=5.9 Hz); 4.09(2H, t, J=5.9 Hz); (1H, d, J=3.4 Hz);6.1(1H, d, J=3.4 Hz); 7.28–7.39(5H, m) 18. —CH₃ H H

Mol. Wt. = 229 Yield = 76% ¹H: 2.23(3H, s); 2.8–2.9(2H, m);2.91–2.99(2H, m); 3.69(2H, t, J=5.8 Hz); 3.86(2H, t, J=5.8 Hz); 5.83(1H,d, J=3.3 Hz); 5.88(1H, d, J=3.6 Hz); 7.17–7.31(5H, m) 19. —CH₃ H H

Mol. Wt. = 231 Yield = 80% ¹H: 2.33(3H, s); 3.64(2H, t, J=6 Hz);3.82(3H, s); 4.11(2H, t, J=6 Hz); 5.9(1H, d, J=3.3 Hz); 6.12(1H, d,J=3.3 Hz); 6.8–7.32(4H, m) 20. —CH₃ H H

Mol. Wt. = 207 Yield = 82% ¹H: 1.24–1.81(10H, m); 2.23(3H, s);2.47–2.52(1H, m); 3.76–3.78(2H, m); 3.94(2H, t, J=6 Hz); 5.79–5.83(2H,m) 21. —CH₃ H H

Mol. Wt. = 277 Yield = 76% ¹H: 2.32(3H, s); 3.6(2H, t, J=6 Hz); 4.09(2H,t, J=6 Hz); (1H, d, J=2.94 Hz); 6.15(1H, d, 3.39 Hz); 7.2–7.6(9H, m) 22.—CH₃ H H

Mol. Wt. = 191 Yield = 70% ¹H: 2.3(3H, s); 3.81–3.83(2H, m); 4.17(2H, t,J=5.8 Hz); 5.93(1H, d, J=3.5 Hz); 6.33(2H, dd, J=3.3 Hz, J₂=3.4 Hz);6.43(1H, dd, J=1.87 Hz, 1.88 Hz); 7.402–7.407(1H, m) 23. —CH₃ H H

Mol. Wt. = 205 Yield = 80% ¹H: 2.30(3H, s); 2.32(3H, s); 3.85(2H, t,J=5.77 Hz); 4.15(2H, t, J=5.8 Hz); 5.9(1H, d, J=3.5 Hz); 6.0(1H, d,J=3.43 Hz); 6.22(1H, d, J=3.09 Hz); 6.27(1H, d, J=3.54 Hz) 24. —CH₃ H H

Mol. Wt. = 247 Yield = 100% ¹H: 2.3(3H, s); 2.49(3H, s); 3.58(2H, t,J=6.03 Hz); 4.0(2H, t, J=6.0 Hz); 5.93–5.94(1H, dd, J₁=0.738 Hz,J₂=0.665 Hz); 6.0(1H, d, J=3.4 Hz); 7.22–7.32(4H, m) 25. —CH₃ H H

Mol. Wt. = 226 Yield = 70% ¹H: 2.34(3H, s); 3.67(2H, t, J=5.9 Hz);4.14(2H, t, J=6 Hz); 6.011(1H, d, J=3.4 Hz); 6.23(1H, d, J=3.5 Hz);7.5(2H, d, J=8.5 Hz); 7.65(2H, d, J=8.5 Hz) 26. —CH₃ H H

Mol. Wt. = 293 Yield = 76% ¹H: 2.33(3H, s); 3.65(2H, t, J=6 Hz);4.09(2H, t, J=6 Hz); 5.9(1H, d, J=3.31 Hz); 6.08(1H, d, J=3.38 Hz);6.99–7.38(9H, m) 27. —CH₃ H H

Mol. Wt. = 344 Yield = 85% ¹H: 2.8(3H, s); 2.4(3H, s); 3.59(2H, t, J=5.7Hz); 3.74(2H, t, J=5.7 Hz); 5.63(1H, d, J=3.4 Hz); 5.86(1H, d, J=3.4Hz); 6.25–6.26(1H, m); 6.31(1H, t, J=3.3 Hz); 7.23(2H, d, J=8.3 Hz);7.43–7.48(3H, m) 28. —CH₃ H H

Mol. Wt. = 261 Yield = 100% ¹H: 2.3(3H, s); 3.65(2H, t, J=5.9 Hz);3.88(3H, s); 3.9(3H, s); 4.06(2H, t, J=6.0 Hz); 5.94–5.95(1H, m) 6.0(1H,d, J=3.1 Hz); 6.87–7.26(3H, m) 29. —CH₃ H H

Mol. Wt. = 258 Yield = 78% ¹H: 2.12(3H, s); 2.3(3H, s); 3.61(2H, t,J=6.03 Hz); 4.15(2H, t, J=6.0 Hz); 5.9(1H, d, J=2.7 Hz); 6.02(1H, d,J=3.3 Hz); 6.7(2H, d, J=8.5 Hz); 7.16(2H, d, J=8.5 Hz) 30. —CH₃ H H

Mol. Wt. = 328 Yield = 92% ¹H: 1.4–1.63(6H, m); 2.3(3H, s); 2.48–2.5(4H,m); 2.75(2H, t, J=6.03 Hz); 3.5(2H, t, J=6.2 Hz); 4.0(2H, t, J=6.3 Hz);4.1(2H, t, J=6.0 Hz); 5.91-5.92(1H, m); 6.0(1H, d, J=3.3 Hz); 6.889(2H,d, J=8.5 Hz); 7.2(2H, d, J=8.5 Hz) 31. —CH₃ H H

Mol. Wt. = 257 Yield = 83% ¹H: 2.3(3H, s); 3.6(2H, t, J=6 Hz); 4.03(2H,t, J=6.1 Hz); 4.55(2H, d, J=5.3 Hz); 5.28–5.32(2H, dd, J=1.35 Hz J₂=1.35 Hz); 5.40–5.46(1H, dd, J=1.56 Hz, J₂=1.5 Hz); 5.93(1H, d, J=3.36Hz); 6.04(1H, d, J=3.42 Hz); 6.93(2H, d, J=8.5 Hz), 7.28(2H, d, J=8.5Hz) 32. —CH₃ H H

Mol. Wt. = 309 Yield = 79% ¹H: 2.3(3H, s); 3.64(2H, t, J=6 Hz); 4.08(2H,t, J=6.09 Hz); 5.96(1H, d, J=3.36 Hz); 6.11(1H, d, J=3.45 Hz);7.25–7.42(9H, m) 33. —CH₃ H H

Mol. Wt. = 279 Yield = 80% ¹H: 2.35(3H, s); 2.08(3H, s) 3.68(2H, t,J=5.7 Hz); 4.17(2H, t, J=5.8 Hz); 6.02(1H, d, J=3.5 Hz); 5.7(1H, d,J=3.5 Hz); 7.6(2H, d, J=8.5 Hz); 7.94(2H, d, J=8.5 Hz) 34. —CH₃ H H

Mol. Wt. = 313 Yield = 89% ¹H: 1.03–1.69(11H, m) 2.3(3H, s); 3.6(2H, t,J=6.0 Hz); 3.7(2H, d, J=6.2 Hz); 4.04(2H, t, J=6 Hz) 5.9(1H, d, J=3.3Hz); 6.0(1H, d, J=3.3 Hz); 6.88(2H, d, J=8.5 Hz); 7.29(2H, d, J=8.5 Hz)35. —CH₃ H H

Mol. Wt. = 207 Yield = 55% ¹H: 2.3(3H, s), 3.74(2H, t, J=3.4 Hz);4.13(2H, t, J=6 Hz); 5.9(1H, d, J=3.4 Hz); 6.2(1H, d, J=3.4 Hz);7.03–7.05(2H, m); 7.25–7.27(1H, m) 36. —CH₃ H H

Mol. Wt. = 307 Yield = 98% ¹H: 2.3(3H, s), 3.58(2H, t, J=6.0 Hz);4.0(2H, t, J=6.0 Hz); 5.0(2H, s); 5.91(1H, d, J=3.3 Hz); 6.0(1H, d,J=3.3 Hz); 6.96–6.99(2H, m); 7.27–7.45(7H, m) 37. H H H

Mol. Wt. = 187 Yield = 99% ¹H: 3.7(2H, t, J=5.4 Hz); 4.1(2H, t, J=5.4Hz); 6.23(2H, m); 6.8(1H, m); 7.4–7.8(5H, m) 38. —CH₃ H H

Mol. Wt. = 165 Yield = 61% ¹H: 0.58–0.61(2H, m); 0.79–0.85(2H, m);1.66–1.7(1H, m); 2.24(3H, s); 3.87(2H, t, J=5.87) Hz; 4.11(2H, t, J=5.89Hz); 5.69(1H, d, J=3.26 Hz); 5.76(1H, d, J=3.2 Hz) 39. —CH₃ H H

Mol. Wt. = 241 Yield = 47% ¹H: 2.36(3H, s); 3.93(2H, t, J=5.77 Hz);4.32(2H, t, J=5.76 Hz); 6.0(1H, d, J=3.63 Hz); 6.57(1H, d, J=3.63 Hz);6.69(1H, s); 7.54–7.2(4H, m) 40. —CH₃ COOCH₃ H

Mol. Wt. = 259 Yield = 92% ¹H: 2.63(3H, s); 3.61–3.63; (2H, m); 3.79(3H,s); 4.07–4.15(2H, m); 6.54(1H, s); 7.34–7.43(5H, m) 41. —CH₃ H H

Mol. Wt. = 241 Yield = 58% ¹H: 2.3(3H, s); 3.74(2H, t, J=5.7 Hz);4.13(2H, t, J=5.9 Hz); 5.9(1H, d, J=3.0 Hz); 6.1(1H, d, J=3.5 Hz);6.8(1H, d, J=3.8 Hz); 6.84(1H, d, J=3.8 Hz) 42. —CH₃ H H

Mol. Wt. = 245 Yield = 99% ¹H: 1.43(3H, t, J=6.97 Hz); 2.33(3H, s);3.6(2H, t, J=5.99 Hz); 4.02(4H, m); 5.94(1H, d, J=3.28 Hz); 6.04(1H, d,J=3.35 Hz); 6.91(2H, d, J=8.69 Hz); 7.28(2H, d, J=8.6.9 Hz) 43. —CH₃ H H

Mol. Wt. = 221 Yield = 93% ¹H: 2.3(3H, s); 2.4(3H, s); 3.74(2H, t,J=6.0) Hz; 4.13(2H, t, J=6 Hz); 5.9(1H, d, J=3.4 Hz); 6.17(1H, d, J=3.4Hz); 6.67(1H, d, J=3.4 Hz); 6.8(1H, d, J=3.4 Hz) 44. —CH₃ CH₃ H C₆H₅Mol. Wt. = 215 Yield = 50% ¹H: 2.06(3H, s); 2.2(3H, s); 3.62(2H, t,J=6); 4.07(2H, t, J=6); 6.0(1H, s); 7.25(1H, m); 7.3–7.4(4H, m) 45. —CH₃H H

Mol. Wt. = 245 Yield = 100% ¹H: 2.32(3H, s); 3.62(2H, t, J=6.03 Hz);4.05(2H, t, J=6.04 Hz); 5.92(1H, d, J=3.27 Hz); 5.98(2H, s); 6.03(1H, d,J=3.36 Hz); 6.84(2H, d, J=8.46 Hz); 7.16(1H, s) 46. —CH₃ H H

Mol. Wt. = 251 Yield = 36% ¹H: 2.37(3H, s); 3.42(2H, t, J=5.85 Hz);3.5–3.8(2H, m); 6.02(1H, d, J=3.27 Hz); 6.15(1H, d, J=3.36 Hz);7.43–7.89(7H, m) 47. —CH₃ H H

Mol. Wt. = 307 Yield = 100% ¹H: 2.31(3H, s); 3.56(2H, t, J=6.03 Hz);4.03(2H, t, J=6.03 Hz); 5.08(2H, s); 5.94(1H, d, J=3.36 Hz); 6.1(1H, d,J=3.39 Hz); 6.93–7.44(9H, m) 48. —CH₃ H H

Mol. Wt. = 286 Yield = 30% ¹H: 2.31(3H, s); 3.76(2H, t, J=5.9 Hz);4.1(2H, t, J=5.9 Hz); 5.9(1H, d, J=3.48 Hz); 6.95(1H, d, J=3.54 Hz);6.7(1H, d, J=3.78 Hz); 6.9(1H, d, J=3.78 Hz). 49. —CH₃ H H

Mol. Wt. = 259 Yield = 100% ¹H: 1.33(6H, d, J=5.13 Hz); 2.94(3H, s);3.60(2H, t, J=6.07 Hz); 4.03(2H, t, J=6.07 Hz); 4.52–4.60(1H, m);5.92(1H, d, J=2.82 Hz); 6.03(1H, d, J=3.36 Hz); 6.88(2H, d, J=8.7 Hz);7.27(2H, d, J=8.67 Hz) 50. —CH₃ H CH₃

Mol. Wt. = 215 Yield = 57% ¹H: 1.97(3H, s); 2.29(3H, s); 3.51(2H, t, J=6Hz); 3.95(2H, t, J=6 Hz); 5.83(1H, s); 7.25–7.43(5H, m) 51. H H H H Mol.Wt. = 111 Yield = 98% — 52. CH₃ H H CH₃ Mol. Wt. = 139 Yield = 65% ¹H:2.21(6H, s); 3.70–3.72(2H, m); 3.89(2H, t, J=5.8 Hz); 5.76(2H, s). 53.i-Pr

H i-Pr Mol. Wt. = 271 Yield = 42% ¹H: 1.25(12H, d, J=6.5 Hz); 2.97(1H,sept, J=6.7 Hz); 3.24(1H, sep, J=6.7 Hz); 3.85(2H, m); 4.1(2H, t, J=7Hz); 5.87(1H, s); 7.19–7.32(5H, m) 54. i-Pr H H

Mol. Wt. = 259 Yield = 84% ¹H: 1.27(6H, d, J=6.5 Hz); 2.99–3.04(1H, m);3.53(2H, t, J=6.15 Hz); 3.82(3H, s); 4.09(2H, t, J=6.2 Hz); 5.96(1H, d,J=3.5 Hz); 6.67(1H, d, J=3.48 Hz); 6.91(2H, d, J=8.9 Hz); 7.29(2H, d,J=8.6 Hz) 55. i-Pr H H

Mol. Wt. = 247 — ¹H: 1.27(6H, d, J=6.0 Hz); 2.97–3.06(1H, m); 3.53(2H,t, J=6.0 Hz); 4.08(2H, t, J=6.0 Hz); 5.99(1H, d, J=3.60 Hz); 6.10(1H, d,J=3.3 Hz); 7.05–7.1(2H, t, J=8.8 Hz); 7.34–7.37(2H, m) 56. i-Pr H

Mol. Wt. = 323.2 Yield = 55% ¹H: 1.34(6H, d, J=7 Hz); 3.09(1H, sep, J=7Hz); 3.57(2H, t, J=4.5 Hz); 4.02(2H, t, J=4.5 Hz); 6.22(1H, s);7.03–7.30(9H, m); 57. i-Pr

Mol. Wt. = 442 Yield = 52% ¹H: 1.47(6H, d, J=7.2 Hz); 3.5–3.6(1H, m);3.59(2H, t, J=6.2 Hz); 3.99(2H, t, J=6.6 Hz); 6.79(1H, s); 6.91–7.0(3H,m); 7.08–7.19(10H, m). 58.

—H H

Mol. Wt. = 281 79 ¹H: 1.55(1H, s); 3.3(2H, dd, J=6.0 Hz); 4.2(2H, t,J=6.0 Hz); 6.25(2H, dd, J=3.6 Hz); 7.1(2H, t, J=7.0 Hz); 7.4(1H, m,J=9.0 Hz); 7.42–7.47(6H, m) 59.

—COOEt H

Mol. Wt. = 353 55 ¹H: 1.10(3H, t, J=7.0 Hz); 1.60(1H, s, OH); 3.35(2H,t, J=6.0 Hz); 4.00(2H, t, J=6.0 Hz); 4.10(2H, t, J=Hz); 6.69(1H, s);7.10(2H, t, J=9.9 Hz); 7.39–7.46(7H, m) 60. i-Pr H H CH₃ Mol. Wt. = 16768 ¹H: 1.2(6H, d, J=8 Hz); 2.2(3H, s); 2.94(1H, septet); 3.77(2H, t,J=6.9 Hz); 3.97(2H, t, J=6.9 Hz); 5.8(2H, s).

PREPARATION 2 1-(2-hydroxyethyl)-2-ethyl-1H-pyrrole (compound no. 61)

A mixture containing 1-(2-bromoethyl)-2-acetyl-1H-pyrrole (8.2 g),ethylene glycol (45 mL), 85% potassium hydroxide pellets (8.91 g) and80% hydrazine hydrate (6.76 mL) was stirred at 200° C. for about 1.5 hralong with simultaneous distillation of volatile materials. The productobtained was extracted with ethyl acetate (2×100 mL). The ethyl acetatelayer was washed with water (100 mL), dried over sodium sulfate,filtered and evaporated. The crude product obtained was purified bycolumn chromatography (silica gel 100–200), using ethyl acetate:pet.ether (8:2) as an eluent to obtain 2.2 g of the title compound.

TABLE 2 Substituents on the pyrrole ring Comp. in (1e) No. R¹ R² R³ R⁴61. C₂H₅ H H H Mol. Wt. = 139 Yield = 42% ¹H: 1.26(3H, t, J=6.0Hz);2.59(2H, q, J₁=7.62Hz, J₂=7.44Hz); 3.84(2H, t, J=5.4Hz); 3.98(2H, t,J=5.35Hz); 5.92–5.93(1H, m); 6.11(1H, t, J=3.12Hz); 6.65(1H, t,J=2.22Hz).

PREPARATION 3 1-(2-Bromoethyl)-1H-pyrrole-2-carbaldehyde (compound no.62)

A mixture of 2-formylpyrrole (1 g), potassium hydroxide (2.3 g) and dryDMSO (20 mL) was stirred under nitrogen atmosphere. 1,2-dibromoethane(7.9 g) was added dropwise at 20–25° C. and stirred till the reaction iscomplete. Water (50 mL) was added and the reaction mixture was extractedwith diethyl ether (3×50 mL). The combined organic layer was washed withwater (30 mL), followed by brine (30 mL) and was dried over Na₂SO₄. Thesolvent was evaporated and the compound obtained was purified by columnchromatography (silica gel 100–200) using ethyl acetate: hexane (2:8) asan eluent to obtain the title compound.

In like manner to that described in Preparation 3, following compoundsof the formula (1c) (Given in Table 3) were prepared from theappropriately substituted pyrrole derivatives. The latter can besynthesized by using various routes found in literature.

TABLE 3 (1c)

Comp. Substituents on the pyrrole ring in (1c) No. R¹ R² R³ R⁴ 62. CHO HH H Mol. Wt. = 202 Yield = 47% ¹H: 3.65(2H, t, J=6 Hz); 4.65(2H, t, J=6Hz); 6.33(1H, m); 6.95–7.05(2H, m); 9.5(1H, m). 63. COCH₃ H H H Mol. Wt.= 216 Yield = 32% ¹H: 2.44(3H, s); 3.67(2H, t, J=6 Hz); 4.65(2H, t, J=6Hz); 6.16–6.18(1H, m); 6.94(1H, t, J=6 Hz); 7.01–7.03(1H, m). 64. —COPhH H H Mol. Wt. = 277 Yield = 66% ¹H: 3.79(2H, t, J=6.08 Hz); 4.75(2H, t,J=6.12 Hz); 6.22(1H, dd, J=2.57 Hz, J₂=2.53 Hz); 6.825(1H, dd, J₁=1.64Hz, J₂=1.67 Hz); 7.06–7.08(1H, m); 7.45–7.80(5H, 1m)

PREPARATION 4 Preparation of 1-(2-hydroxyethyl)-2-methylthio-1H-pyrrole(compound no. 65)

To a mixture of potassium hydroxide (7.9 g) and dry DMSO (90 mL),2-thiomethylpyrrole (4 g) was added dropwise at 20–25° C., with stirringunder nitrogen atmosphere. Stirring was continued for 1 hr at 20–25° C.Ethyl bromoacetate (11.85 g) was added dropwise at 20–25° C. andstirring was continued for 2 hr. In the reaction mixture (100 mL) DMwater was added and pH was made acidic (pH=3) with 20% HCl (30 mL). Thereaction mixture was extracted with diethyl ether (2×50 mL). Thecombined organic extract was washed with DM water (50 mL), saturatedbrine (50 mL) and dried over Na₂SO₄. The solvent was evaporated toobtain 2-thiomethylpyrrol-1-yl-acetic acid (4.5 g).

To a suspension of sodium borohydride (1.77 g) in tetrahydrofuran (50mL), 2-thiomethylpyrrol-1-yl-acetic acid (4 g) dissolved in THF (50 mL)was added dropwise at 20° C.–25° C. within 10–15 min under nitrogenatmosphere. When the evolution of hydrogen gas ceases, the reactionmixture was cooled to 5–10° C. and iodine (5.94 g) dissolved in THF (20mL) was added dropwise at 5° C.–10° C. and was stirred further for 2 hrsat 20° C.–25° C. The reaction mixture poured in mixture of ice-cold KOHsolution (10 mL) and DM water (50 mL). The solution was extracted withethyl acetate (2×50 mL). The organic extract was washed with water (30mL), brine (30 mL) and dried over Na₂SO₄. The solvent was evaporatedunder reduced pressure, to obtain the title compound.

In like manner to that described in Preparation 4, following compoundsof the formula (1e) (Given in Table 4) were prepared from theappropriately substituted pyrrole. The latter can be synthesized byusing various routes found in literature.

TABLE 4 (1e)

Comp. Substituents on the pyrrole ring in (1e) No. R¹ R² R³ R⁴ 65. SCH₃H H H Mol. Wt. = 157 Yield = 90% ¹H: 2.2(3H, s); 3.85(2H, t, J=6.0 Hz);4.1(2H, t, J=5.5 Hz); 6.14(1H, dd); 6.38(1H, dd); 6.85(1H, dd) 66.

H CH₃ H Mol. Wt. = 201 Yield = 13% ¹H: 2.05(3H, s); 3.75(2H, t, J=6 Hz);4.03(2H, t, J=5.5 Hz); 6.07(1H, s); 6.62(1H, s); 7.27–7.42(5H, m). 67.CH₃ H

H Mol. Wt. = 201 Yield = 57% ¹H: 2.24(3H, s); 3.82–4.01(4H, m); 6.19(1H,s); 6.9(1H, s); 7.1–7.4(5H, m). 68. CH₃ H CH₃ H Mol. Wt. = 139 Yield =40.4% ¹H: 2.02(3H, s); 2.19(3H, s); 3.7–3.9(4H, m); 5.73(1H, s);6.38(1H, s).

PREPARATION 5 Preparation of Methyl2-(5-ethyl-2-phenyl-1H-pyrrol-1-yl)ethane sulfonate (Compound No. 90)

To a solution of compound 17 (4.0 g in 30 mL dichloromethane) obtainedin preparation 1, triethylamine (2.75 mL) was added followed by additionof methanesulfonyl chloride (2.1 g) at 0° C. The reaction mixture wasstirred at 0° C. for 1 h under nitrogen atmosphere. The mixture waswarmed to temperature of about 20 to 25° C. and was stirred at thattemperature for about 2 h (TLC). After the completion of the reaction,water (30 mL) was added and the organic layer was separated. The mixturewas washed with saturated sodium bicarbonate solution (20 mL), water (20mL) and then with brine (20 mL) and dried over Na₂SO₄. The organic layerwas concentrated under reduced pressure. The crude substance was used inthe next step without purification.

In like manner to that described in Preparation 5 following compounds ofthe formula (1c) (given in Table 5) were prepared from the appropriatelysubstituted pyrrole derivatives (1e) described earlier.

TABLE 5 (1e)

Comp. Substituents on the pyrrole ring in (1c) No. R¹ R² R³ R⁴ 69. CH₃ HCH₃ H Mol. Wt. = 217 Yield = 98% — 70. C₂H₅ H H H Mol. Wt. = 217 Yield =90% ¹H: 1.29(3H, t, J=2.64 Hz); 2.58(2H, q, J=7.32 Hz); 2.71(3H, s);4.15(2H, t, J=5.52 Hz); 4.41(2H, t, J=5.5 Hz); 5.92(1H, m); 6.11(1H, t,J=3.16 Hz); 6.63(1H, t, J=2.26 Hz). 71. CH₃ H H CH₂CH₃ Mol. Wt. = 231Yield = 56% ¹H: 1.26(3H, t, J=7.4 Hz); 2.25(3H, m) 2.57(2H, q, J=7.42Hz); 2.69(3H, s); 4.12(2H, t, J=5.9 Hz); 4.34(2H, t, J=5.9 Hz);5.8–5.83(2H, m). 72. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 246 Yield = 45% ¹H:1.02(3H, t, J=7 Hz); 1.65(2H, m); 2.25(3H, s); 2.5(2H, t, J=7.7 Hz);2.69(3H, s); 4.1(2H, t, J=5.9 Hz); 4.35(2H, t, J=5.9 Hz); 5.8–5.83(2H,m) 73. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 259 Yield = 72% ¹H: 0.95(3H, t,J=7.2 Hz); 1.44–1.46(2H, m); 1.58–1.62(2H, m); 2.25(3H, s); 2.5(2H, t,J=5.9 Hz); 2.7(3H, s); 4.1(2H, t, J=5.9 Hz); 4.39(2H, t, J=5.9 Hz);5.8(2H, s). 74. CH₃ H H

Mol. Wt. 279 Yield = 98% ¹H: 2.34(3H, s); 2.83(3H, s); 4.11(2H, t, J=5.7Hz); 4.27(2H, t, J=5.7 Hz); 5.96(1H, d, J=3.4 Hz); 6.10(1H, d, J=3.4Hz); 7.27–7.43(5H, m). 75. CH₃ H

H Mol. Wt. = 279 Yield = 86% ¹H: 2.28(3H, s); 2.73(3H, m); 4.16(2H, d,J=5.4 Hz); 4.4(2H, d, J=5.4 Hz); 6.2(1H, s); 6.9(1H, s); 7.17(1H, d,J=6.75 Hz); 7.3(2H, d, J=7.0 Hz); 7.46(2H, d, J=7.0 Hz). 76. CH₃ H H

Mol. Wt. = 293 Yield = 68% ¹H: 2.33(3H, s); 2.38(3H, s); 2.65(3H, s);4.12(2H, t, J=6.3 Hz); 4.25(2H, t, J=6.3 Hz); 5.95(1H, d, J=3.4 Hz);6.10(1H, d, J=3.4 Hz); 7.19–7.25(4H, m). 77. CH₃ H H

Mol. Wt. = 293 Yield = 95% ¹H: 2.33(3H, s); 2.38(3H, s); 2.66(3H, s);4.12(2H, t, J=5.8 Hz); 4.27(2H, t, J=5.7 Hz); 5.95(1H, d, J=3.37 Hz);6.09(1H, d, J=3.42 Hz); 7.12–7.16(2H, m); 7.25–7.31(2H, m). 78. CH₃ H H

Mol. Wt. = 293 Yield = 55% ¹H: 2.34(3H, s); 2.38(3H, s); 2.67(3H, s);4.13(2H, t, J=5.8 Hz); 4.27(2H, t, J=5.7 Hz); 5.96(1H, d, J=3.36 Hz);6.1(1H, d, J=3.39 Hz); 7.13–7.29(4H, m). 79. CH₃ H H

Mol. Wt. = 309 Yield = 62% ¹H: 2.3(3H, s); 2.67(3H, s); 3.8(3H, s);4.12(2H, t, J=5.45 Hz); 4.24(2H, t, J=5.45 Hz); 5.9(1H, d, J=3.39 Hz);6.0(1H, d, J=3.39 Hz); 6.95(2H, d, J=6.78 Hz); 7.26(2H, d, J=6.78 Hz).80. CH₃ H H

Mol. Wt. = 358 Yield = 70% ¹H: 2.33(3H, s); 2.7(3H, s); 4.13–4.15(2H,m); 4.2–4.25(2H, m); 5.97(1H, d, J=3.4 Hz); 6.12(1H, d, J=3.4 Hz);7.21–7.26(2H, m); 7.52–7.55(2H, m). 81. CH₃ H H

Mol. Wt. = 297 Yield = 90% ¹H: 2.3(3H, s); 2.7(3H, s); 3.6(2H, t, J=6.0Hz); 4.1(2H, d, J=5.6 Hz); 4.22(2H, d, J=5.4 Hz); 5.9(1H, d, J=3.4 Hz);6.0(1H, d, J=3.4 Hz); 7.04–7.1(2H, m); 7.2–7.3(2H, m). 82. CH₃ H H

Mol. Wt. = 313.5 Yield = 82% ¹H: 2.3(3H, s); 2.69(3H, s); 4.15(2H, d,J=6.3 Hz); 4.25(2H, d, J=6.3 Hz); 5.96–5.97(1H, dd); 6.1(1H, d, J=3.4Hz); 7.27–7.4(4H, m). 83.

H CH₃ H Mol. Wt. = 279 Yield = 90% ¹H: 2.13(3H, s); 2.73(3H, m);4.2–4.28(4H, m); 6.05(1H, s); 6.59(1H, s); 7.29–7.43(5H, m). 84. CH₃ H

Mol. Wt. = 355 Yield = 90% ¹H: 2.3(3H, s); 2.73(3H, s); 4.09–4.14(4H,m); 6.2(1H, s); 7.0–7.4(10H, m). 85. i-Pr H H i-Pr Mol. Wt. = 272 Yield= 37% ¹H: 1.23–1.25(12H, d, J=6.7 Hz); 2.76(3H, s); 2.82–2.99(2H, m);4.18(2H, m); 4.33(2H, m); 5.86(2H, s) 86. i-Pr H H

Mol. Wt. = 307 Yield = 100% ¹H: 1.30(6H, t, J=6.78 Hz); 2.65(3H, m);2.96–3.00(1H, m); 4.04(2H, t, J=6 Hz); 4.32(2H, t, J=6 Hz); 6.0(1H, d,J=3.54 Hz); 6.12(1H, d, J=3.54 Hz); 7.32–7.43(5H, m). 87. i-Pr

H

Mol. Wt. = 444 Yield = 15% ¹H: 1.5–1.52(6H, d, J=7.1 Hz); 2.84(3H, s);3.44–3.52(1H, m); 4.12–4.15(2H, t, J=6.4 Hz); 4.3–4.34(2H, t, J=6.4 Hz);6.32(1H, s); 7.12–7.18(3H, t, J=8.5 Hz); 7.3–7.4(4H, m); 7.56–7.59(2H,d, J=7.6 Hz). 88. SCH₃ H H H Mol. Wt. = 235 Yield = 95% ¹H: 2.29(3H, s);2.77(3H, s); 4.35–4.48(4H, m); 6.17(1H, dd); 6.4(1H, dd); 6.85(1H, dd).89. C₂H₅ H H C₂H₅ Mol. Wt. = 245 Yield = 82% ¹H: 1.27(6H, t, 7.3 Hz);2.58(4H, q, J=7.4 Hz); 2.7(3H, s); 4.11(2H, t, J=6.04 Hz); 4.34(2H, t,J=6.2 Hz); 5.8(2H, s) 90. C₂H₅ H H

Mol. Wt. = 293 Yield = 92% ¹H: 1.33(3H, t, J=7.3 Hz); 2.6–2.7(5H, m);4.1(2H, t, J=5.9 Hz); 4.28(2H, t, J=5.9 Hz); 5.9(1H, d, J=3.59 Hz);6.1(1H, d, J=3.48 Hz); 7.3–7.43(5H, m) 91. CH₃ H H

Mol. Wt. = 307 Yield = 96% ¹H: 2.24(3H, s); 2.65(3H, s); 2.8–2.85(2H,m); 2.94–2.99(2H, m); 4.03(2H, t, J=5.8 Hz); 4.28(2H, t, J=5.8 Hz);5.84(1H, d, J=3.39 Hz); 5.9(1H, d, J=3.39 Hz); 7.18–7.23(3H, m),7.31–7.32(2H, m) 92. CH₃ H H

Mol. Wt. = 309 Yield = 75% ¹H: 2.34(3H, s); 2.68(3H, s); 3.83(3H, s);4.16(2H, t, J=5.6 Hz); 4.29(2H, t, J=5.9 Hz); 5.96(1H, d, J=3.36 Hz);6.12(1H, d, J=3.42 Hz); 6.94–7.34(4H, m) 93. CH₃ H H

Mol. Wt. = 285 Yield = 84% ¹H: 1.21–1.88(10H, m); 2.24(3H, s)2.24–2.45(1H, m); 2.7(3H, s); 4.12(2H, t, J=5.94 Hz); 4.34(2H, t, J=6Hz); 5.79–5.83(2H, m) 94. CH₃ H H

Mol. Wt. = 355 Yield = 74% ¹H: 2.35(3H, s); 2.68(3H, s); 4.17(2H, t,J=5.59 Hz); 4.33(2H, t, J=5.55 Hz); 5.99(1H, d, J=2.49 Hz); 6.12(1H, d,J=3.18 Hz); 7.2–7.65(9H, m) 95. CH₃ H H

Mol. Wt. = 269 Yield = 84% ¹H: 2.31(3H, s), 2.69(3H, s); 4.35(2H, t,J=5.2 Hz); 4.43(2H, J=4.9 Hz); 5.91–5.92(1H, dd, J1=0.68 Hz, J2=0.73Hz); 6.3(2H, d, J=3.5 Hz); 6.35(1H, d, J=2.8 Hz); 7.41–7.42(1H, dd,J1=0.7 Hz, J2=0.65 Hz) 96. CH₃ H H

Mol. Wt. = 283 Yield = 90% ¹H: 2.30(3H, s); 2.32(3H, s); 2.68(3H, s),3.88(2H, t, J=5.2 Hz); 4.20(2H, t, J=4.9 Hz); 5.93(1H, d, J=3.5 Hz);6.33(1H, d, J=3.5 Hz); 6.22(1H, d, J=3.09 Hz); 6.27(1H, d, J=3.54 Hz)97. CH₃ H H

Mol. Wt. = 325 Yield = 80% ¹H: 2.33(3H, s); 2.5(3H, s); 2.68(3H, s);4.14(2H, t, J=5.82 Hz); 4.25(2H, t, J=5.64 Hz); 5.96(1H, d, J=3.33 Hz);6.0(1H, d, J=3.4 Hz); 7.25–7.27(4H, m) 98. CH₃ H H

Mol. Wt. = 304 Yield = 90% ¹H: 2.36(3H, s); 2.73(3H, s); 4.16(2H, t,J=5.6 Hz); 4.32(2H, t, J=5.8 Hz), 6.03(1H, d, J=3.5 Hz); 6,238(1H, d,J=3.54 Hz); 7.45(2H, d, J=8.5 Hz); 7.69(2H, d, J=8.5 Hz) 99. CH₃ H H

Mol. Wt. = 371 Yield = 85% ¹H: 2.33(3H, s); 2.69(3H, s); 4.15(2H, t,J=5.5 Hz); 4.26(2H, t, J=5.7 Hz); 5.96(1H, d, J=3.29 Hz); 6.09(1H, d,J=3.4 Hz); 7.0–7.39(9H, m) 100. CH₃ H H

Mol. Wt. = 422 Yield = 93% ¹H: 2.3(3H, s); 2.4(3H, s); 2.75(3H, s);3.96(2H, t, J=5.8 Hz); 4.18(2H, t, J=5.98 Hz); 5.68(1H, d, J=3.47 Hz);5.86(1H, d, J=3.38 Hz); 6.27–6.28(1H, dd, J1=1.72 Hz, J2=1.75 Hz);6.32(1H, t, J=3.3 Hz); 7.18(2H, d, J=8.3 Hz); 7.41(2H, d, J=8.3 Hz);7.46–7.47(1H, dd, J1=1.7 Hz, J2=1.72 Hz) 101. CH₃ H H

Mol. Wt. = 339 Yield = 78% ¹H: 2.26(3H, s); 2.7(3H, s); 3.89(3H, s);3.92(3H, s); 4.15–4.25(4H, m); 5.95(1H, d, J=3.0 Hz); 6.0(1H, d, J=3.1Hz); 6.87–7.26(3H, m) 102. CH₃ H H

Mol. Wt. = 336 Yield = 90% ¹H: 2.1(3H, s); 2.29(3H, s); 2.69(3H, s);4.11(2H, t, J=5.35 Hz); 4.27(2H, t, J=5.6 Hz); 7.29(2H, d, J=8.5 Hz);7.58(2H, d, J=8.5 Hz)(no peak of py. proton) 103. CH₃ H H

Mol. Wt. = 406 Yield = 93% ¹H: 1.45–1.65(6H, m); 2.32(3H, s);2.51–2.52(4H, m); 2.67(3H, s); 2.8(2H, t, J=6 Hz); 4.1–4.15(4H, m);4.2(2H, t, J=5.5 Hz); 5.9(1H, d, J=3.33 Hz); 6.0(1H, d, J=3.4 Hz);6.96(2H, d, J=8.5 Hz); 7.26(2H, d, J=8.5 Hz) 104. CH₃ H H

Mol. Wt. = 335 Yield = 73% ¹H: 2.32(3H, s); 2.67(3H, s); 4.14(2H, t,J=5.3 Hz); 4.23(2H, t, J=5.5 Hz); 4.57(2H, d, J=5.3 Hz) Hz;5.32–5.47(1H, dd, J₁=1.35 Hz, J₂=1.53 Hz); 5.4–5.48(1H, dd, J=1.5 Hz,1.5 Hz); 5.9(1H, d, J=3.36 Hz); 6.05(1H, d, J=3.42 Hz); 6.08–6.14(1H,m); 6.94(2H, d, J=8.5 Hz); 6.728(2H, d, J=8.5 Hz) 105. CH₃ H H

Mol. Wt. = 357 Yield = 93% ¹H: 2.36(3H, s); 2.74(3H, s); 3.1(3H, s);4.15(2H, t, J=5.86 Hz); 4.34(2H, t, J=5.83 Hz); 6.03(1H, d, J=3.5 Hz);6.25(1H, d, J=3.54 Hz); 7.5(2H, d, J=8.5 Hz); 7.97(2H, d, J=8.5 Hz) 106.CH₃ H H

Mol. Wt. = 391 Yield = 90% ¹H: 1.03–1.69(11H, m); 2.3(3H, s); 2.67(3H,s); 3.7(2H, t, J=6.24 Hz); 4.11(2H, t, J=3.3 Hz); 4.2(2H, t, J=3.3 Hz);5.9(1H, d, J=3.39 Hz); 6.04(1H, d, J=3.39 Hz); 6.91(2H, d, J=8.5 Hz);7.24(2H, d, J=8.5 Hz) 107. CH₃ H H

Mol. Wt. = 285 Yield = 94% ¹H: 2.3(3H, s); 2.6(3H, s); 4.29(4H, m);5.9(1H, d, J=3.4 Hz); 6.2(1H, d, J=3.4 Hz); 6.9–7.01(1H, m);7.05–7.06(1H, m); 7.29(1H, m) 108. CH₃ H H

Mol. Wt. = 385 ¹H: 2.3(3H, s); 2.7(3H, s); 4.13(2H, t, J=5.3 Hz);4.2(2H, t, J=5.3 Hz); 5.09(2H, s); 5.9(1H, d, J=3.3 Hz); 6.0(1H, d,J=3.3 Hz); 7.0(2H, d, J=8.7 Hz); 7.25–7.46; (7H, m) 109. H H H C₆H₅ Mol.Wt. = 265 Yield = 40% ¹H: 2.7(3H, s); 4.12(4H, m); 6.22(2H, m); 6.8(1H,m); 7.3–7.9(5H, m) 110. CH₃ H H

Mol. Wt. = 320 Yield = 98% ¹H: 2.3(3H, s); 2.75(3H, s); 4.29(4H, m);5.9(1H, d, J=3.4 Hz); 6.2(1H, d, J=3.5 Hz); 6.78(1H, d, J=3.78 Hz);6.88(1H, d, J=3.4 Hz) 111. CH₃ H H

Mol. Wt. = 323 Yield = 99% ¹H: 1.44(3H, t, J=6.98 Hz); 2.33(3H, s);2.67(3H, s); 4.05(2H, t, J=6.98 Hz); 4.09(2H, t, J=5.0 Hz); 4.22(2H, m);5.94(1H, d, J=3.24 Hz); 6.04(1H, d, J=3.34 Hz); 6.93(2H, d, J=9.43 Hz);7.26(2H d, J=8.63 Hz) 112. CH₃ H H

Mol. Wt. = 299 96% ¹H: 2.3(3H, s); 2.4(3H, s); 2.69(3H, s); 4.29(4H, s);5.9(1H, d, J=3.4 Hz); 6.17(1H, d, J=3.5 Hz); 6.7(1H, d, J=3.4 Hz);6.77(1H, d, J=3.4 Hz) 113. CH₃ CH₃ H C₆H₅ Mol. Wt. = 293 Yield = 92% ¹H:2.04(3H, s); 2.24(3H, s); 2.67(3H, s); 4.12(2H, t, J=5.6 Hz); 4.24(2H,t, J=5.6 Hz); 6.01(1H, s); 7.2–7.4(5H, m) 114. CH₃ H H

Mol. Wt. = 243 Yield = 95% ¹H: 0.59–0.62(2H, m); 0.82–0.87(2H, m);1.5–1.6(1H, m); 2.24(3H, s); 2.69(3H, s); 4.27(2H, t, J=5.9 Hz);4.45(2H, t, J=5.8 Hz), 5.68(1H, d, J=3.3 Hz); 5.75(1H, d, J=3.34 Hz)115. CH₃ H H

Mol. Wt. = 319 Yield = 81% ¹H: 2.36(3H, s); 2.73(3H, s); 3.93(2H, t,J=5.77 Hz); 4.32(2H, t, J=5.76 Hz); 6.0(1H, d, J=3.63 Hz); 6.57(1H, d,J=3.63 Hz); 6.69(1H, s); 7.54–7.72(4H, m) 116. CH₃ COOCH₃ H

Mol. Wt. = 337 Yield = 84% ¹H: 2.64(3H, s); 2.73(3H, s); 3.81(3H, s);4.11(2H, t, J=5.76 Hz); 4.29(2H, t, J=5.76 Hz); 6.56(1H, s);7.26–7.45(5H, m). 117. CH₃ H H

Mol. Wt. = 323 Yield = 85% ¹H: 2.32(3H, s); 2.7(3H, s); 4.14(2H, t,J=5.37 Hz), 4.23(2H, t, J=5.47 Hz); 5.92(1H, d, J=2.85 Hz); 6.0(2H, s);6.03(1H, d, J=3.39 Hz); 6.74–6.86(3H, m) 118. CH₃ H H

Mol. Wt. = 329 Yield = 97% ¹H: 2.39(3H, s); 2.59(3H, s); 3.91–3.98(2H,m); 4.1–4.16(2H, m); 6.07(1H, d, J=3.33 Hz); 6.17(1H, d, J=3.36 Hz);7.43–7.90(7H, m) 119. CH₃ H H

Mol. Wt. = 385 Yield = 100% ¹H: 2.31(3H, s); 2.62(3H, s); 4.06(2H, t,J=5.56 Hz); 4.18(2H, t, J=5.65 Hz); 5.1(2H, s); 5.94(1H, d, J=3.03 Hz);6.1(1H, d, J=3.42 Hz); 6.92–7.44(9H, m) 120. CH₃ H H

Mol. Wt. = 364 Yield = 96% ¹H: 2.32(3H, s); 2.73(3H, s); 4.28(4H, s);5.9(1H, d, J=3.5 Hz); 6.2(1H, d, J=3.54 Hz); 6.7(1H, d, J=3.75 Hz);7.02(1H, d, J=3.81 Hz) 121. CH₃ H H

Mol. Wt. = 337 Yield = 100% ¹H: 1.36(6H, d, J=6.03 Hz); 2.32(3H, s);2.66(3H, s); 4.13(2H, t, J=5.29 Hz); 4.22(2H, t, J=5.53 Hz);4.53–4.61(1H, m); 5.92(1H, d, J=3.36 Hz); 6.03(1H, d, J=3.39 Hz);6.90(2H, d, J=8.7 Hz); 7.24(2H, d, J=8.1 Hz) 122. CH₃ H CH₃

Mol. Wt. = 293 Yield = 95% ¹H: 1.88(3H, s); 2.29(3H, s); 2.68(3H, s);4.03(2H, t, J=5.26 Hz); 4.13(2H, t, J=5.61 Hz); 5.83(1H, s);7.26–7.45(5H, m) 123. H H H H Mol. Wt. = 189 Yield = 26% ¹H: 2.7(3H, s);4.19(2H, t, J=5.2 Hz); 4.43(2H, t, J=5.2 Hz); 6.17(2H, t, J=2.1 Hz);6.7(2H, t, J=2.1 Hz); 124. CH₃ H H CH₃ Mol. Wt. = 217 Yield = 64% ¹H:2.23(6H, s); 2.68(3H, s); 4.08(2H, t, J=5.8 Hz); 4.34(2H, t, J=5.8 Hz);5.78(2H, s) 125. i-Pr

H i-Pr Mol. Wt. = 349 Yield = 97% — 126. i-Pr H H

Mol. Wt. = 337 Yield = 99% — 127. i-Pr H H

Mol. Wt. = 325 Yield = 72% ¹H: 1.29(6H, d, J=6.0 Hz); 2.69(3H, s);2.92–2.99(1H, m); 4.05(2H, t, J=6.0 Hz); 4.27(2H, t, J=6.0 Hz); 6.00(1H,d, J=3.4 Hz); 6.1(1H, d, J=3.4 Hz); 7.07–7.1(2H, t, J=6.0 Hz);7.30–7.35(2H, m) 128. i-Pr H

Mol. Wt. = 369 Yield = 61% ¹H: 1.35(6H, d, J=7 Hz); 2.76(3H, s);3.0–3.05(1H, m); 4.05(2H, t, J=6.2 Hz); 4.15(2H, t, J=6 Hz); 6.22(1H,s); 7.07–7.30(9H, m) 129. i-Pr

Mol. Wt. = 520 Yield = 85% — 130. i-Pr

Mol. Wt. = 534 Yield = 100% — 131.

H H

Mol. Wt. = 359 Yield = 98% — 132.

—COOEt H

Mol. Wt. = 431 Yield = 98.3% — 133. i-Pr H H CH₃ Mol. Wt. = 245 Yield =97.1% ¹H: 1.28(6H, d, J=7.7 Hz); 2.25(3H, s); 2.7(3H, s); 2.83–2.92(1H,m); 4.14(2H, t, J=6.9 Hz); 4.34(2H, t, J=6.9 Hz); 5.83(2H, s).

PREPARATION 6 4-[2-(5-Methyl-2-phenylpyrrol-1-yl)ethoxy]benzaldehyde(compound No. 134)

To a suspension of potassium carbonate (16.43 g) in dimethyl formamide(50 mL), 4-hydroxy benzaldehyde (4.37 g) was added and warmed to 90° C.to 95° C. To the solution, methyl1-[5-methyl-2-phenyl-1H-pyrrol-1yl]ethane sulfonate (10 g) (compound no.74 dissolved in dimethyl formamide (50 mL) was added within 30 min andthe reaction was continued for further 4 hours. The reaction mixture wasdiluted with water (100 mL) and was extracted with ethyl acetate (3×100mL), washed with water (3×100 mL), brine (200 mL), and was dried oversodium sulfate. The solvent was evaporated under reduced pressure, toyield the title compound.

TABLE 6 (1h)

Comp. Substituents on the pyrrole ring in (1p) No. R¹ R² R³ R⁴ 134. CH₃H H Phenyl Mol. Wt. = 306 Yield = 99% ¹H: 2.39(3H, s); 4.0(2H, t, J=6.3Hz); 4.35(2H, t, J=6.3 Hz); 5.98(1H, d, J=3.4 Hz); 6.12(1H, t, J=3.4Hz); 6.74(2H, d, J=8.7); 7.38–7.42(5H, m); 7.73–7.75(2H, d, J=8.8 Hz);9.85(1H, s).

PREPARATION 7 (S)-Ethyl 3-{4-[2-(2-ethyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example 5)

A mixture of (S)-ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (2.24 g)and dry potassium carbonate (3.7 g) in dimethyl formamide (30 mL) wasstirred at 80° C. for 30 min. Compound. No. 71(Table 5) (2.27 g) wasadded at 40° C. and stirring was continued at 80° C. for 24 h. Thereaction mixture was cooled to 20° C.–25° C. and 20 mL water was added.The reaction mixture was extracted with ethyl acetate (2×40 mL), washedwith water (2×40 mL), brine (40 mL) and was dried over sodium sulfate.The organic layer was evaporated under reduced pressure to obtain anoily product. The crude oily product was chromatographed over silica gel(100–200 mesh) using ethyl acetate: petroleum ether (1:9) as an eluentto afford the title compound as a yellow oil (1.654 g, 45%).

PREPARATION 8 (S)-Ethyl3-{4-[2-(2-formylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate (Example3)

A mixture of (S)-ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (1.12 g)and dry potassium carbonate (2.37 g) in dimethyl formamide (20 mL) wasstirred at 80° C. for 30 min. 1-(2-bromoethyl)2-carbaldehyde pyrrole(1.0 g, Compound. No. 62) was added at 40° C. and stirring was continuedat 80° C. for 24 h. The reaction mixture was cooled to 20° C.–25° C. and20 mL water was added. The reaction mixture was extracted with ethylacetate (2×25 mL), washed with water (2×20 mL), brine (25 mL) and wasdried over sodium sulfate. The organic layer was evaporated underreduced pressure to obtain an oily product. The crude oily product waschromatographed over silica gel (100–200 mesh) using ethylacetate:petroleum ether (1:9) as an eluent to afford the title compoundas a yellow oil (0.4 g, 22%).

PREPARATION 9 (S)-Ethyl3-{4-[2-(5-ethyl-2-phenyllpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoate(Example 24)

A mixture of (S)-ethyl 3-(4-hydroxyphenyl)-2-ethoxypropionate (2.3 g),and dry potassium carbonate (2.6 g) in toluene (15 mL) was heated toreflux for 45 min with continuous removal of water using a Dean-Starkwater separation. The mixture was cooled to 50° C. and mesylate compoundNo. 90 (Table 5) (2.9 g) was added. The reaction mixture was continuedto reflux for 24 hrs. Later it was cooled to 20° C.–25° C. and toluenewas distilled at reduced pressure. To the residue, DM water (30 mL) wasadded and the crude product was extracted with ethyl acetate (2×25 mL),washed with water (2×20 mL), brine (25 mL) and was dried over sodiumsulfate. The solvent was evaporated under reduced pressure to obtain anoily product. The crude oily product was chromatographed over silica gelusing ethyl acetate:petroleum ether (60–80) (1:9) as an eluent to affordthe title product as a yellow oil (73%).

In like manner to that described in preparation 7–9, the followingcompounds of the formula (I) (given in Table 7) were prepared fromappropriately substituted pyrrole derivatives. described in either Table5 or obtained from other methods described herein.

TABLE 7 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 1. CH₃ H CH₃H Mol. Wt. = 359 Yield = 18% ¹H: 1.15(3H, t, J=7 Hz); 1.26(3H, t, J=7Hz); 2.04(3H, s); 2.23(3H, s); 2.91–2.94(2H, m); 3.3–3.39(1H, m);3.5–3.62(1H, m); 3.92(1H, dd, J=6.0 Hz); 4.12–4.2(6H, m); 5.7(1H, s);6.4(1H, s); 6.77(2H, d, J=8.6 Hz); 7.15(2H, d, J=8.6 Hz). 2. C₂H₅ H H HMol. Wt. = 359 Yield = 18% ¹H: 1.15(3H, t, J=7.02 Hz); 1.22(3H, t,J=5.74 Hz); 1.26(3H, t, J=6.03 Hz); 2.62(2H, q); 2.93(2H, d, J=5.7 Hz);3.3–3.4(1H, m); 3.5–3.6(1H, m); 3.94(2H, t, J=6.0 Hz); 4.12–4.20(5H, m);5.91(1H, m); 6.10(1H, t, J=3.12 Hz); 6.69–6.75(1H, m); 6.76(2H, d, J=6.7Hz); 7.13(2H, d, J=8.61 Hz). 3. CHO H H H Mol. Wt. = 359 Yield = 22% ¹H:1.1(3H, t, J=6.9 Hz); 1.26(3H, t, J=6.9 Hz); 2.94–4.08(5H, m);4.08–4.1(2H, m); 4.22(2H, t, J=4.9 Hz); 4.7(2H, t, J=4.9 Hz); 6.23(1H,d); 6.7(2H, d, J=8.5 Hz); 6.97(1H, dd); 7.1(1H, dd); 7.4(2H, d, J=8.5Hz); 9.5(1H, s). 4. COCH₃ H H H Mol. Wt. = 137 Yield = 10% ¹H: 1.15(3H,t, J=3.48 Hz); 1.2(3H, t, J=5.1 Hz); 2.44(3H, s); 2.93(2H, dd, J=5.55Hz); 3.0–3.35(2H, m); 3.94(2H, t, J=3.58 Hz); 4.16(2H, q, J₁=1.44 Hz,J₂=1.41 Hz); 4.21(1H, t, J=5.04 Hz); 4.69(2H, t, J=4.99 Hz);6.14–6.15(1H, m); 6.75(2H, d, J=8.37 Hz); 6.99–7.01(2H, m) 7.11(2H, d,J=8.64 Hz). 5. CH₃ H H CH₂CH₃ Mol. Wt. = 373 Yield = 45% ¹H: 1.15(3H, t,J=7 Hz); 1.22(3H, t, J=7 Hz); 1.27(3H, t, J=7 Hz); 2.28(3H, m); 2.63(2H,q, J=7.4 Hz); 2.9–2.96(2H, m); 3.3–3.6(2H, m); 3.92–4.19(7H, m);5.8–5.83(2H, m); 6.75(2H, d, J=6.78 Hz); 7.14(2H, d, J=6.78 Hz). 6. CH₃H H (CH₂)₂CH₃ Mol. Wt. = 389 Yield = 41% ¹H: 1.02(3H, t, J=6.9 Hz);1.15(3H, t, J=6.9 Hz); 1.23(3H, t, J=7.14 Hz); 1.65–1.7(2H, m); 2.28(3H,s); 2.5(2H, t, J=7.75 Hz); 2.9–2.92(2H, m); 3.25–3.5(2H, m); 3.94(1H, t,J=3.66 Hz); 4.0–4.2(6H, m) 5.8–5.83(2H, m); 6.75(2H, d, J=8.5 Hz);7.15(2H, d, J=8.5 Hz). 7. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 401 Yield = 46%¹H: 0.95(3H, t, J=7.2 Hz); 1.15(3H, t, J=7 Hz); 1.23(3H, t, J=7 Hz);1.4–1.47(2H, m); 1.6–1.7(2H, m); 2.28(3H, s); 2.5(2H, t, J=7.7 Hz);2.9–2.97(2H, m); 3.3–3.39(1H, m); 3.55–3.63(1H, m); 4.04–4.22(7H, m);5.8–5.83(2H, m); 6.7(2H, d, J=8.5 Hz); 7.15(2H, d, J=8.5 Hz). 8. CH₃ H H

Mol. Wt. = 421 Yield = 85% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.37(3H, s); 2.9–2.92(2H, dd); 3.32–3.35(1H, m); 3.5–3.58(1H, m);3.9–3.92(3H, m); 4.12–4.19(2H, q); 4.28(2H, t, J=6.5 Hz); 5.96–5.97(1H,d, J=3.1 Hz); 6.1–6.11(1H, d, J=3.11 Hz); 6.6(2H, d, J=8.5 Hz);7.06–7.09(2H, d, J=8.5 Hz); 7.3–7.4(5H, m). 9. CH₃ H

H Mol. Wt. = 421 Yield = 63% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t,J=7.1 Hz); 2.37(3H, s); 2.9–2.92(2H, m); 3.3–3.4(1H, m); 3.53–3.62(1H,m); 3.9(1H, t, J=6.6 Hz); 4.1–4.22(6H, m); 6.2(1H, s); 6.8(2H, d, J=8.5Hz); 6.98(1H, s); 7.15(2H, d, J=8.5 Hz); 7.23–7.33(3H, m); 7.4(2H, t,J=7.1 Hz). 10. CH₃ H H

Mol. Wt. = 435 Yield = 34% ¹H: 1.16(3H, t, J=6.9 Hz); 1.22(3H, t, J=6.9Hz); 2.37(3H, s); 2.39(3H, s); 2.9–2.92(2H, m); 3.3–3.37(1H, m);3.56–3.62(1H, m); 3.91–4.2(5H, m); 4.27(2H, m); 5.95(1H, d, J=3.36 Hz);6.10(1H, d, J=3.36 Hz); 6.6(2H, d, J=8.5 Hz); 7.0(2H, d, J=6.78 Hz);7.19(2H, d, J=8.5 Hz); 7.28(2H, d, J=6.78 Hz). 11. CH₃ H H

Mol. Wt. = 435 Yield = 37% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.13Hz); 2.37(6H, s); 2.91(2H, d, J=5.94 Hz); 3.89–3.95(5H, m); 4.15(2H, q,J₁=7.11 Hz, J₂=7.11 Hz); 4.28(2H, t, J=6.63 Hz); 5.95(1H, d, J=3.39 Hz);6.07(1H, d, J=3.39 Hz); 6.59(2H, d, J=7.62 Hz); 7.07(2H, d, J=8.64 Hz);7.15–7.28(4H, m). 12. CH₃ H H

Mol. Wt. = 435 Yield = 53% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.13Hz); 2.37(6H, s); 2.9–2.92(2H, m); 3.3–3.58(2H, m); 3.89–3.95(3H, m);4.15(2H, t, J=6 Hz); 4.28(2H, t, J=6 Hz); 5.95(1H, d, J=3.2 Hz); 6.0(1H,d, J=3.2 Hz); 6.6(2H, d, J=7.62 Hz); 7.0(2H, d, J=8.64 Hz);7.12–7.28(4H, m). 13. CH₃ H H

Mol. Wt. = 451 Yield = 41% ¹H: 1.1(3H, t, J=7 Hz); 1.22(3H, t, J=7 Hz);2.36(3H, s); 2.9–2.92(2H, dd); 3.3–3.32(1H, m); 3.52–3.62(1H, m);3.84(3H, m); 3.9–3.94(3H, m); 4.14(2H, t, J=6.68 Hz); 4.22(2H, t, J=6.68Hz); 5.9(1H, d, J=3.36 Hz); 6.0(1H, d, J=3.36 Hz); 6.64(2H, d, J=8.58Hz); 6.95(2H, d, J=6.78 Hz); 7.10(2H, d, J=8.5 Hz); 7.31(2H, d, J=6.78Hz). 14. CH₃ H H

Mol. Wt. = 500 Yield = 40% ¹H: 1.15(3H, t, J=7 Hz); 1.2(3H, t, J=7 Hz);2.37(3H, s); 2.95(2H, dd); 3.29–3.38(1H, m); 3.55–3.63(1H, m);3.9–3.95(3H, m); 4.17(2H, t, J=6.3 Hz); 4.28(2H, t, J=6.3 Hz); 5.9(1H,d, J=3.42 Hz); 6.1(1H, d, J=3.42 Hz); 6.6(2H, d, J=8.5 Hz); 7.21(2H, d,J=8.5 Hz); 7.29(2H, d, J=8.5 Hz); 7.5(2H, d, J=8.5 Hz). 15. CH₃ H H

Mol. Wt. = 439 Yield = 30% ¹H: 1.15(3H, t, J=6.99 Hz); 1.23(3H, t,J=6.99 Hz); 1.58(3H, s); 2.9–2.93(2H, dd); 3.3–3.4(1H, m); 3.55–3.65(1H,m); 3.85–4.0(3H, m); 4.1–4.2(2H, m); 4.24(2H, t, J=6.4 Hz); 5.9(1H, d,J=3.3); 6.0(1H, d, J=3.4 Hz); 6.6(2H, t, J=8.6 Hz); 7.0–7.1(4H, m);7.26–7.38(2H, m). 16. CH₃ H H

Mol. Wt. = 455.5 Yield = 62% ¹H: 1.15(3H, t, J=7 Hz); 1.23(3H, t, J=7Hz); 2.36(3H, s); 2.9–2.95(2H, dd); 3.33–3.4(1H, m); 3.53–3.62(1H, m);3.9–4.13(3H, m); 4.18(2H, t, J=6.3 Hz); 4.26(2H, t, J=6.3 Hz); 5.97(1H,d, J=3.27 Hz); 6.1(1H, d, J=3.4 Hz); 6.6(2H, d, J=8.4 Hz); 7.1(2H, d,J=8.4 Hz); 7.25–7.38(2H, m); 7.4(2H, d, J=8.5 Hz). 17.

H CH₃ H Mol. Wt. = 421 Yield = 13% ¹H: 1.15(3H, t, J=6.9 Hz); 1.23(3H,t, J=7.2 Hz); 2.13(3H, s); 2.92(2H, d); 3.33(1H, m); 3.59(1H, m);3.94(3H, m); 4.07–4.26(4H, m); 6.05(1H, s); 6.67–6.72(3H, m); 7.12(2H,m); 7.3–7.43(5H, m). 18. CH₃ H

Mol. Wt. = 497 Yield = 32% ¹H: 1.153(3H, t, J=7.0 Hz); 1.24(3H, t, J=7Hz); 2.4(3H, s); 2.9–2.92(2H, m); 3.33–3.36(1H, m); 3.53–3.63(1H, m);3.85–3.95(3H, m); 4.1–4.2(4H, m); 6.2(1H, s); 6.5–7.4(14H, m). 19. i-PrH H i-Pr Mol. Wt. = 415 Yield = 36% ¹H: 1.15(3H, t, J=6.9 Hz); 1.23(3H,t, J=7.0 Hz); 1.24–1.26(12H, d, J=6.7 Hz); 2.9(4H, m); 3.35 1(H);3.6(1H, m); 3.95(1H, m); 4.05(2H, t); 4.1–4.2(2H, q, J₁=6.8 Hz, J₂=7.1Hz); 4.23(2H, t, J=6.6 Hz); 5.87(2H, s); 6.75–6.76(2H, d, J=8.6 H);7.12–7.15(2H, d, J=8.6 Hz) 20. i-Pr H H

Mol. Wt. = 449 Yield = 31% ¹H: 1.14(3H, t, J=6.99 Hz); 1.21(3H, t,J=5.55 Hz); 1.31(6H, d, J=6.15 Hz); 2.90(2H, d, J=6.15 Hz); 3.1(1H, m);3.32–3.57(2H, m); 3.84(2H, t, J=6.75 Hz); 3.91(1H, t, J=3.55 Hz);4.12–4.19(2H, q, J₁=7.14 Hz, J₂=7.14 Hz); 4.33(2H, t, J=6.8 Hz);6.00(1H, d, J=3.51 Hz); 6.12(1H, d, J=3.51 Hz); 6.53(2H, d, J=8.64 Hz);7.05(2H, d, J=8.61 Hz); 7.31 7.40(5H, m). 21. i-Pr

H

Mol. Wt. = 586 Yield = 20% ¹H: 1.15(3H, t, J=6.9 Hz); 1.23(3H, t, J=7.1Hz); 1.51–1.53(6H, d, J=7.1 Hz); 2.92(2H, dd, J=7.11 Hz); 3.33–3.4(1H,m); 3.5–3.6(2H, Complex); 3.9–4.0(3H, m); 4.1–4.2(2H, q, J=7.11 Hz);4.3–4.4(2H, t, J=6.3 Hz); 6.31(1H, s); 6.58–6.61(2H, d, J=8.5 Hz);7.0–7.2(4H, m); 7.3–7.4(4H, m); 7.5(1H, s); 7.6(2H, d, J=7.6 Hz) 22.SCH₃ H H H Mol. Wt. = 377 Yield = 20% ¹H: 1.14(3H, t, J=7.0 Hz);1.24(3H, t, J=7.0 Hz); 2.29(3H, s); 2.90–2.94(2H, m); 3.30–3.40(1H, m);3.54–3.62(1H, m); 3.95(1H, t, J=3.6 Hz); 4.13–4.22(4H, m); 4.40(2H, t,J=5.6 Hz); 6.15(2H, d, J=3.2 Hz); 6.37(1H, dd); 6.80(2H, d, J=8.5 Hz);6.94(1H, m); 7.15(2H, d, J=8.5 Hz). 23. C₂H₅ H H C₂H₅ Mol. Wt. = 387Yield = 73% ¹H: 1.15(3H, t, J=7 Hz); 1.25(3H, t, J=7 Hz); 1.28(6H, t,J=7.3 Hz); 2.64(4H, t, J=7.4 Hz); 2.92–2.94(2H, m); 3.29–3.38(1H, m);3.53–3.61(1H, m); 3.94(1H, t, J=1.38 Hz); 4.07(2H, t, J=5.97 Hz);4.12–4.21(4H, m); 5.8(2H, s); 6.7(2H, d, J=8.6 Hz); 7.15(2H, d, J=8.6Hz) 24. C₂H₅ H H C₆H₅ Mol. Wt. = 435 Yield = 73% ¹H: 1.15(3H, t, J=6.9Hz); 1.22(3H, t, J=7.1 Hz); 1.24(3H, t, J=7.3 Hz); 2.73(2H, q, 2≈7.4Hz); 2.9–3.1(2H, m); 3.28–3.38(1H, m); 3.53–3.61(1H, m); 3.88–3.95(3H,m); 4.19(2H, t, J=7.1 Hz); 4.29(2H, t, J=7.2 Hz); 6.0(1H, d, J=3.42 Hz);6.15(1H, d, J=3.45 Hz); 6.59(2H, d, J=8.5 Hz); 7.0(2H, d, J=8.5 Hz);7.3–7.4(5H, m) 25. CH₃ H H

Mol. Wt. = 449 Yield = 72% ¹H: 1.15(3H, t, J=6.9 Hz); 1.25(3H, t, J=7Hz); 2.29(3H, s); 2.9–2.97(6H, m); 3.29–3.37(1H, m); 3.53–3.62(1H, m);3.9–4.2(7H, m); 5.85(1H, d, J=3.1 Hz); 5.9(1H, d, J=3.37 Hz); 6.73(2H,d, J=8.6 Hz); 7.13(2H, J=8.6 Hz); 7.21–7.3(5H, m) 26. CH₃ H H

Mol. Wt. = 497 Yield = 60% ¹H: 1.14(3H, t, J=6.9 Hz); 1.23(3H, t, J=7.1Hz); 2.39(3H, s); 2.9(2H, d, J=6.1 Hz); 3.28–3.38(1H, m); 3.53–3.61(1H,m); 3.92–4.2(5H, m); 4.34(2H, t, J=6.5 Hz); 5.9(1H, d, J=3.3 Hz);6.17(1H, d, J=3.4 Hz); 6.6(2H, d, J=8.5 Hz); 7.0(2H, d, J=8.5 Hz);7.43–7.5(5H, m); 7.6–7.68(4H, m) 27. CH₃ H H

Mol. Wt. = 411 Yield = 60% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7Hz); 2.35(3H, s); 2.91–2.94(2H, m); 3.29–3.38(1H, m); 3.53–3.63(1H, m);3.9(1H, t, J=6.0 Hz); 4.12–4.2(4H, m); 4.4(2H, t, J=6.4 Hz);5.91–5.92(1H, m); 6.31–6.38(2H, m); 6.42–6.45(1H, m); 6.7(2H, d, J=8.6Hz); 7.13(2H, d, J=8.5 Hz); 7.41–7.42(1H, m) 28. CH₃ H H

Mol. Wt. = 467 Yield = 80% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.29(3H, s); 2.3(3H, s); 2.92(2H, d, J=7.26 Hz); 3.28–3.38(1H, m);3.53–3.61(1H, m); 3.89–3.97(3H, m); 4.19(2H, t, J=7 Hz); 4.29(2H, t,J=6.55 Hz); 5.96(1H, d, J=3.36 Hz); 6.0(1H, d, J=3.39 Hz); 6.6(2H, d,J=8.5 Hz); 7.0(2H, d, J=8.5 Hz); 7.22–7.33,(4H, m) 29. CH₃ H H

Mol. Wt. = 425 Yield = 60% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.29(3H, s); 2.3(3H, s); 2.94(2H, d, J=7.26 Hz); 3.3–3.38(1H, m);3.54–3.63(1H, m); 3.94(1H, t, J=6.0 Hz); 4.12–4.19(4H, m); 4.36(2H, t,J=6.4 Hz); 5.91(1H, d, J=3.4 Hz); 5.9–6.0(1H, m); 6.22(1H, d, J=3.06Hz); 6.26(1H, d, J=3.5 Hz); 6.7(2H, d, J=8.6 Hz), 7.13-(2H, d, J=8.58Hz) 30. CH₃ H H

Mol. Wt. = 446 Yield = 70% ¹H: 1.15(3H, t, J=6.69 Hz); 1.23(3H, t, J=7Hz); 2.38(3H, s); 2.91–2.95(2H, m); 3.3–3.40(1H, m); 3.54–3.64(1H, m);3.9–3.98(3H, m); 4.16(2H, q, J=7.1 Hz); 4.34(2H, t, J=6.18 Hz); 6.0(1H,d, J=3.48 Hz); 6.2(1H, d, J=3.54 Hz); 6.62(2H, d, J=8.6 Hz); 6.75(2H, d,J=8.49 Hz); 7.5(2H, d, J=8.37 Hz); 7.67(2H, d, J=8.3 Hz) 31. CH₃ H H

Mol. Wt. = 513 Yield = 60% ¹H: 1.15(3H, t, J=7 Hz); 1.22(3H, t, J=6.9Hz); 2.37(3H, s); 2.93(2H, d, J=7 Hz); 3.29–3.38(1H, m); 3.54–3.62(1H,m); 3.94(3H, t, J=6.2 Hz); 4.17(2H, q, J=7 Hz); 4.28(2H, t, J=6.3 Hz);5.96(1H, d, J=3.3 Hz); 6.08(1H, d, J=3.39 Hz); 6.64(2H, d, J=8.6 Hz);7.0–7.4(11H, m) 32. CH₃ H H

Mol. Wt. = 564 Yield = 30% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.28(3H, s); 2.3(3H, s); 2.95(2H, d, J=6.5 Hz); 3.3–3.38(1H, m);3.54–3.62(1H, m); 3.86–4.2(7H, m); 5.7(1H, d, J=3.48 Hz); 5.88–7.8(1H,m) 33. CH₃ H H

Mol. Wt. = 481 Yield = 64% ¹H: 1.15,(3H, t, J=6.9 Hz); 1.22(3H, t, J=9Hz); 2.37(3H, s); 2.9–2.92(2H, m); 3.28–3.35(1H, m); 3.55–3.62(1H, m);3.86(3H, s); 3.91(3H, s); 3.9–3.95(3H, m); 4.17(2H, q, J=7.1 Hz);4.27(2H, t, J=6.6 Hz); 5.96(1H, d, J=3.39 Hz); 6.0(1H, d, J=3.39 Hz);6.64(2H, d, J=8.5 Hz); 6.91–6.94(3H, m); 7.1(2H, d, J=8.5 Hz) 34. CH₃ HH

Mol. Wt. = 483 Yield = 90% ¹H: 1.15,(3H, t, J=6.9 Hz); 1.22(3H, t, J=9Hz); 2.38(3H, s); 2.90–2.93(2H, m); 2.77(3H, s); 3.28–3.38(1H, m);3.54–3.62(1H, m); 3.9–3.99(3H, m); 4.17(2H, q, J=7.1 Hz); 4.34(2H, t,J=6.3 Hz); 5.9(1H, d, J=3.48 Hz); 6.18(1H, d, J=3.48 Hz); 6.64(2H, d,J=8.6 Hz); 7.11(2H, d, J=8.6 Hz); 7.58(2H, d, J=8.4 Hz); 7.66(2H, d,J=8.4 Hz) 35. CH₃ H H

Mol. Wt. = 464 Yield = 40% ¹H: 1.15(3H, t, J=7.0 Hz); 1.22(3H, t, J=6.9Hz); 2.32(3H, s); 2.8–2.9(2H, m); 3.23–3.4(1H, m); 3.48–3.59(1H, m);3.64(3H, s); 3.9(2H, t, J=6.0 Hz); 3.9–4.0(3H, m); 4.28(2H, t, J=6.0Hz); 5.85(1H, d, J=3.28 Hz); 5.96(1H, d, J=3.4 Hz); 6.58(2H, d, J=8.6Hz); 7.02(2H, d, J=8.5 Hz); 7.32(2H, J=8.5 Hz); 7.57(2H, d, J=8.5 Hz)36. CH₃ H H

Mol. Wt. = 548 Yield = 60% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=6.9Hz); 1.4–1.7(6H, m); 2.36(3H, s); 2.5–2.55(4H, m); 2.79(2H, t, J=6.06Hz); 2.9–2.95(2H, m); 3.3–3.41(1H, m); 3.53–3.62(1H, m); 3.88–3.98(3H,m); 4.1–4.2(4H, m); 4.26(2H, t, J=6 Hz); 5.94(1H, d, J=3.1 Hz); 6.0(1H,d, J=3.1 Hz); 6.6(2H, d, J=8.5 Hz); 6.94(2H, d, J=8.5 Hz); 7.1(2H, d,J=8.5 Hz); 7.31(2H, d, J=8.6 Hz) 37. CH₃ H H

Mol. Wt. = 477 Yield = 50% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.36(3H, s); 2.9(2H, d, J=7.1 Hz); 3.28–3.99(1H, m); 3.53–3.63(1H,m); 3.91(3H, t, J=6.6 Hz); 4.15(2H, q, J=7.1 Hz); 4.25(2H, t, J=6.6 Hz);4.56(2H, d, J=3.9 Hz); 5.29–5.34(1H, dd); 5.4–5.5(1H, dd); 5.94(1H, d,J=2.9 Hz); 6.05(1H, d, J=3.48 Hz); 6.08–6.13(1H, m); 6.63(2H, d, J=8.6Hz); 6.95(2H, d, J=8.7 Hz); 7.09(2H, d, J=8.5 Hz); 7.3(2H, d, J=8.69Hz); 38. CH₃ H H

Mol. Wt. = 529 Yield = 50% ¹H: 1.15(3H, t, J=7 Hz); 1.22(3H, t, J=7 Hz);2.36(3H, s); 2.90–2.91(2H, m); 3.29–3.38(1H, m); 3.53–3.61(1H, m);3.94(3H, t, J=6.25 Hz); 4.19(2H, q, J=7 Hz); 4.3(2H, t, J=6.3 Hz);5.9(1H, d, 3.3 Hz); 6.11(1H, J=3.4 Hz); 6.6(2H, d, J=8.67 Hz); 7.1(2H,d, J=8.6 Hz); 7.26–7.42(9H, m) 39. CH₃ H H

Mol. Wt. = 545 Yield = 80% ¹H: 1.15(3H, t, J=7 Hz); 1.22(3H, t, J=7 Hz);2.36(3H, s); 2.9–2.93(2H, m); 3.3–3.39(1H, m); 3.52–3.64(1H, m);3.91–3.94(3H, m); 4.26(2H, t, J=6.0 Hz); 4.3(2H, t, J=6.0 Hz); 5.97(1H,d, J=3.6 Hz); 6.14(1H, d, J=3.48 Hz); 6.6(2H, J=8.6 Hz); 7.09(2H, d,J=8.5 Hz); 7.46–7.7(9H, m) 40. CH₃ H H

Mol. Wt. = 499 Yield = 75% ¹H: 1.15(3H, t, J=7 Hz); 1.22(3H, t, J=7 Hz);2.39(3H, s); 2.9–3.0(2H, m); 3.09(3H, s); 3.4–3.62(2H, m); 3.91–3.94(3H,m); 4.26(2H, t, J=6.0 Hz); 4.3(2H, t, J=6 Hz); 6.02(1H, d, J=3.3 Hz);6.2(1H, d, J=3.5 Hz); 6.6(2H, d, J=8.58 Hz); 7.11(2H, d, J=8.5 Hz);7.6(2H, d, J=8.4 Hz); 7.9(2H, d, J=8.4 Hz) 41. CH₃ H H

Mol. Wt. = 533 Yield = 64% ¹H: 1.12–1.29(6H, m); 1.15(3H, t, J=7 Hz);1.22(3H, t, J=7 Hz); 1.56–1.86(5H, m); 2.35(3H, s); 2.9(2H, d, J=7.05Hz); 3.3–3.38(1H, m); 3.53–3.62(1H, m); 3.78(2H, d, J=6.18 Hz);3.89–3.97(3H, m); 4.17(2H, t, J=7.1 Hz); 4.23(2H, t, J=7 Hz); 5.9(1H, d,J=3.3 Hz); 6.04(1H, d, J=3.36 Hz); 6.62(2H, d, J=8.6 Hz); 6.92(2H, d,J=8.7 Hz); 7.09(2H, d, J=8.58 Hz); 7.3(2H, d, J=8.7 Hz) 42. COPh H H HMol. Wt. = 435 Yield = 45% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 2.95(2H, d, J=6.6 Hz); 3.3–3.4(1H, m); 3.51–3.62(1H, m);3.95–4.2(7H, m); 5.66–6.15(2H, m); 6.72–6.75(1H, m); 6.74(2H, d, J=8.5Hz); 6.8–7.96(7H, m) 43. CH₃ H H

Mol. Wt. = 385 Yield = 60% ¹H: 0.6–0.62(2H, m); 0.81–0.84(2H, m);1.15(3H, t, J=6.99 Hz); 1.23(3H, t, J=7.1 Hz); 1.7(1H, m); 2.27(3H, s);2.94(2H, d, J=5.64 Hz); 3.3–3.9(2H, m); 3.95–3.96(1H, m); 4.12–4.2(4H,m); 4.32(2H, t, J=6.43 Hz); 5.7(1H, d, J=3.3 Hz); 5.76(1H, d, J=3.3 Hz);6.76(2H, d, J=8.61 Hz); 7.14(2H, d, J=8.58 Hz) 44. CH₃ H H

Mol. Wt. = 461 Yield = 41.5% ¹H: 1.14(3H, t, J=6.98 Hz); 1.21(3H, t,J=6.04 Hz); 2.39(3H, s); 2.92(2H, d, J=6 Hz); 3.57–3.32(2H, m); 3.92(1H,t, J=3.56 Hz); 4.15(2H, q, J₁=7.13 Hz, J₂= 7.12 Hz); 4.23(2H, t, J=6.06Hz); 4.53(2H, t, J=6.05 Hz); 5.99(1H, d, J=3.5 Hz); 6.56(1H, d, J=3.6Hz); 6.69(1H, s); 6.73(2H, d, J=8.59 Hz); 7.1(2H, d, J=8.56 Hz);7.54–8.2(4H, m) 45. CH₃ COOCH₃ H

Mol. Wt. = 479 Yield = 33% ¹H: 1.12–1.28(6H, m); 2.69(3H, s); 2.91(2H,d, J=5.8 Hz); 3.32(2H, m); 3.8(3H, s); 3.8–3.93(3H, m); 4.11–4.19(2H,m); 4.3(2H, t, J=6.18 Hz); 6.54–6.61(3H, m); 7.07(2H, d, J=8.58 Hz);7.36–7.44(5H, m) 46. CH₃ H H

Mol. Wt. = 465 Yield = 28% ¹H: 1.15(3H, t, J=6.99 Hz); 1.22(3H, t,J=7.12 Hz); 2.35(3H, s); 2.92(2H, d, J=5.91 Hz); 3.0–3.8(2H, m);3.89–3.95(3H, m); 4.12–4.17(2H, q, J₁=7.11 Hz, J₂= 7.11 Hz); 4.25(2H, t,J=6.72); 5.93(1H, d, J=3.33 Hz); 5.99(2H, s); 6.03(1H, d, J=3.39 Hz);6.62(2H, d, J=8.67 Hz); 6.84–6.88(3H, m); 7(2H, d, J=8.64 Hz) 47. CH₃ HH

Mol. Wt. = 417 Yield = 56% ¹H: 1.16(3H, t, J=6.16 Hz); 1.23(3H, t,J=7.81 Hz); 2.43(3H, s); 2.87(2H, d, J=6.84 Hz); 2.9–3.3(2H, m);3.74(2H, t, J=6.48 Hz); 3.89(2H, t, J=6.64 Hz); 4.1–4.18(3H, m);6.06(1H, d, J=3.33 Hz); 6.15(1H, d, J=3.36 Hz); 6.38(2H, d, J=8.61 Hz);6.98(2H, d, J=8.58 Hz); 7.41–7.9(7H, m) 48. CH₃ H H

Mol. Wt. = 527 Yield = 42% ¹H: 1.14(3H, t, J=6.99 Hz); 1.22(3H, t,J=7.14 Hz); 2.36(3H, s); 2.89–2.92(2H, m); 3.0–3.85(2H, m);3.86–3.92(3H, m); 4.15(2H, q, J₁=7.14 Hz, J₂=7.10 Hz); 4.23(2H, t,J=6.42 Hz); 5.08(2H, s); 5.94(1H, d, J=3.27); 6.1(1H, d, J=3.39 Hz);6.6(2H, d, J=8.61 Hz); 6.98–7.05(3H, m); 7.08(2H, d, J=8.58 Hz);7.3–7.4(6H, m) 49. CH₃ H H

Mol. Wt. = 506 Yield = 50% ¹H: 1.15(3H, t, J=6.99 Hz); 1.123(3H, t,J=7.14 Hz); 2.35(3H, s); 2.92(2H, m); 3.33–3.59(2H, m); 3.94(1H, t,J=6.7 Hz); 4.04(2H, t, J=6.22 Hz); 4.13–4.2(2H, q, J₁=7.11 Hz, J₂=7.11Hz); 4.31(2H, t, J=6.24 Hz); 5.92(1H, d, J=3.48 Hz); 6.2(1H, d, J=3.51Hz); 6.7(2H, d, J=8.61 Hz); 6.78(1H, d, J=3.78 Hz); 6.99(1H, d, J=3.75Hz); 7.12(2H, d, J=8.58 Hz) 50. CH₃ H H

Mol. Wt. = 479 Yield = 60% ¹H: 1.15(3H, t, J=6 Hz); 1.22(3H, t, J=6 Hz);1.36(6H, d, J=6.06 Hz); 2.36(3H, s); 2.91(2H, d, J=7.11 Hz);3.33–3.58(2H, m); 3.89–3.95(3H, m); 4.12–4.26(4H, m); 4.3–4.57(1H, m);5.93(1H, d, J=3.33 Hz); 6.04(1H, d, J=3.39 Hz); 6.62(2H, d, J=8.61 Hz);6.90(2H, d, J=8.67 Hz); 7.07(2H, d, J=8.55 Hz); 7.26(2H, d, J=8.28 Hz)51. CH₃ H CH₃

Mol. Wt. = 435 Yield = 49% ¹H: 1.15(3H, t, J=6.9 Hz); 1.21(3H, t, J=7.1Hz); 1.91(3H, s); 2.33(3H, s); 2.90(2H, d, J=7.02 Hz) 3.32–3.58(2H, m);3.83(2H, t, J=6.67 Hz); 3.90–3.95(1H, m); 4.10–4.19(4H, m); 5.84(1H, s);6.54(2H, d, J=8.64 Hz); 7.05(2H, d, J=8.61 Hz); 7.30–7.42(5H, m) 52. MeH H

Mol. Wt. = 427 Yield = 42% ¹H: 1.15(3H, t, J=6.9 Hz), 1.23(3H, t, J=7Hz), 2.36(3H, s); 2.9(2H, m), 3.3(1H, m); 3.6(1H, m); 3.9(1H, m);4.05(2H, t, J=6.4 Hz), 4.12–4.2(2H, q, J₁=J₂=7 Hz); 4.3(2H, t, J=6.4Hz); 5.9(1H, d, J=3.5 Hz); 6.2(1H, d, J=3.5 Hz); 6.6(2H, d, J=8.6 Hz);7.0–7.1(2H, m), 7.12–7.15(2H, m); 7.25–7.27(1H, m) 53. CH₃ H H

Mol. Wt. = 527 Yield = 52% ¹H: 1.15(3H, t, J=6.9 Hz); 1.23(3H, t,J=6.9); 2.3(3H, s); 2.90–2.93(2H, m); 3.3(1H, m); 3.55(1H, m); 3.9(2H,m) 4.1–4.15(3H, m); 4.2(2H, m); 5.1(2H, s); 5.9(1H, d, J=3.3 Hz);6.0(1H, d, J=3.3 Hz); 6.6(2H, d, J=8.5 Hz); 6.99(2H, d, J=8.5 Hz);7.1(2H, d, J=8.5 Hz); 7.3–7.47(7H, m) 54. CH₃ H H

Mol. Wt. = 437 Yield = 50% ¹H: 1.17(3H, t, J=6.9 Hz); 1.23(3H, t, J=7Hz); 2.3(3H, s); 2.9(2H, m); 3.3(1H, m); 3.6(1H, m); 3.9–4.0(3H, m);4.1–4.2(4H, m); 5.9(1H, d, J=3.3 Hz); 6.0(1H, d, J=3.3 Hz); 6.5(2H, d,J=8.6 Hz); 6.8(2H, d, J=8.6 Hz); 7.0(2H, d, J=8.6 Hz); 7.2(2H, d, J=8.6Hz) 55. H H H C₆H₅ Mol. Wt. = 407 Yield = 99% ¹H: 1.15(3H, t, J=6.9 Hz);1.22(3H, J=7.11 Hz); 2.9(2H, m); 3.3–3.4(1H, m); 3.55–3.6(1H, m);3.9(1H, m); 4.08(2H, t, J=6.1 Hz); 4.12–4.17(2H, q; J₁=J₂=7.1 Hz);4.3(2H, t, J=5 Hz); 6.0(2H, m); 6.6(2H, d, J=8.6 Hz); 6.9(1H, m);7.0(2H, d, J=8.6 Hz); 7.1–7.4(5H, m) 56. CH₃ H H

Mol. Wt. = 461.5 Yield = 60% ¹H: 1.1(3H, t, J=6.9 Hz); 1.23(3H, t, J=7Hz); 2.36(3H, s); 2.9(2H, m); 3.3(1H, m); 3.6(1H, m); 3.9(1H, t, J=5.9Hz); 4.05(2H, t, J=6.1 Hz); 4.16(2H, q, J=7 Hz); 4.3(2H, t, J=6.3 Hz),5.9(1H, d, J=3.5 Hz); 6.2(1H, d, J=3.5 Hz); 6.6(2H, d, J=8.6 Hz);6.8(1H, d, J=3.8); 6.86(1H, d, J=3.8 Hz) 7.12(2H, d, J=8.58 Hz) 57. CH₃H H

Mol. Wt. = 465 Yield = 56% ¹H: 1.15(3H, t, J=7.14 Hz); 1.2(3H, t, J=7.14Hz); 1.45(3H, t, J=6.99 Hz); 2.36(3H, s); 2.9(2H, d, J=5.97 Hz);3.35(1H, m); 3.6(1H, m); 3.91(3H, m); 4.15(4H, m); 4.23(2H, m); 5.94(1H,d, J=3.30 Hz); 6.05(1H, d, J=3.33 Hz); 6.62(2H, d, J=8.64 Hz); 6.92(2H,d, J=6.78 Hz); 7.08(2H, d, J=8.64 Hz); 7.3(2H, d, J=6.69 Hz) 58. CH₃ H H

Mol. Wt. = 441 Yield = 53% ¹H: 1.15(3H, t, J=6.99 Hz); 1.23(3H, t, J=7Hz); 2.36(3H, s); 2.48(3H, s); 2.93(2H, d, J=6.17 Hz); 3.33–3.59(2H, m);3.9(1H, t, J=6.6 Hz); 4.05(2H, t, J=6.4 Hz); 4.15(2H, t, J₁=6.4 Hz, J₂=7Hz); 4.32(2H, t, J=6.4 Hz); 5.91(1H, d, J=3.38 Hz); 6.17(1H, d, J=3.4Hz); 6.68–6.71(3H, m); 6.8(1H, d); 7.1(2H, d, J=8.2 Hz) 59. CH₃ CH₃ HC₆H₅ Mol. Wt. = 435 Yield = 51% ¹H: 1.15(3H, t, J=7 Hz) Hz; 1.22(3H, t,J=7 Hz); 2.05(3H, s); 2.27(3H, s); 2.9(2H, m); 3.3(1H, m); 3.5(1H, m);3.9(3H, m); 4.1(2H, m); 4.26(2H, t, J=6.6 Hz); 6.0(1H, S); 6.6(2H, d,J=8.6 Hz); 7.05(2H, d, J=8.5 Hz); 7.26(1H, m); 7.29–7.35(4H, m) 60. CH₃H H

Mol. Wt. = 451 Yield = 70% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7Hz); 2.37(3H, s); 2.9–2.95(2H, m); 3.29–3.38(1H, m); 3.55–3.63(1H, m);3.8(3H, s); 3.94(3H, t, J=6.24 Hz); 4.17(2H, q, J=7.1 Hz); 4.3(2H, t,J=6.6 Hz); 5.96(1H, d, J=2.8 Hz); 6.12(1H, d, J=3.39 Hz); 6.69(2H, d,J=8.6 Hz); 6.88–7.0(2H, m); 7.09(2H, d, J=8.6 Hz); 7.26–7.31(2H, m) 61.CH₃ H H

Mol. Wt. = 427 Yield = 54% ¹H: 1.16(3H, t, J=6.9 Hz); 1.23(3H, t, J=7Hz); 1.3–1.88(10H, m); 2.27(3H, s); 2.51–2.53(1H, m); 2.92–2.95(2H, m);3.3–3.4(1H, m); 3.53–3.63(1H, m); 3.95(1H, t, J=5.9 Hz); 4.0–4.1(2H, m);4.1–4.22(4H, m); 5.8(1H, d, J=3.4 Hz); 5.84(1H, d, J=3.3 Hz); 6.7(2H, d,J=8.6 Hz); 7.13(2H, d, J=8.5 Hz) 62. H H H H Mol. Wt. = 331 Yield = 37%¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=6.9 Hz); 2.94(2H, dd);3.33–3.38(1H, m); 3.54–3.65(1H, m); 3.95(1H, dd); 4.12–4.26(6H, m);6.16(2H, t, J=2.1 Hz); 6.7(2H, t, J=2.1 Hz); 6.8(2H, d, J=8.5 Hz);7.15(2H, d, J=8.5 Hz). 63. CH₃ H H CH₃ Mol. Wt. = 359 Yield = 57% ¹H:1.15(3H, t, J=6.9 Hz); 1.25(3H, t, J=6.9 Hz); 2.27(6H, s); 2.91–2.94(2H,m); 3.32–3.60(2H, m); 3.97–4.2(7H, m); 5.78(2H, s); 6.78(2H, d, J=8.5Hz); 7.15(2H, d, J=8.5 Hz). 64. i-Pr

H i-Pr Mol. Wt. = 491 Yield = 35% ¹H: 1.16(3H, t, J=6.9 Hz);1.2–1.3(15H, m); 2.94–2.96(3H, m); 3.31–3.34(2H, m); 3.96(2H, t, J=6.9Hz); 4.1–4.2(4H, m); 4.3(2H, t, J=6.9); 5.89(1H, s); 6.8(2H, d, J=8.5Hz); 7.15(2H, d, J=8.5 Hz); 7.2–7.33(5H, m) 65. i-Pr H H

Mol. Wt. = 479 Yield = 33% ¹H: 1.1(3H, t, J=7 Hz); 1.2(3H, t, J=7 Hz);1.31(6H, d, J=6 Hz); 3.0–3.1(1H, m); 2.90(2H, dd); 3.33(2H, m); 3.8(3H,s); 3.85(2H, t,); 3.92(1H, t); 4.12–4.16(2H, q, J=7.14 Hz); 4.28(2H, t,J=6.8 Hz); 5.98(1H, d, J=3.4 Hz); 6.07(1H, d, J=3.5 Hz); 6.56(2H, d,J=8.6 Hz); 6.93(2H, d, J=8.7 Hz); 7.32(2H, d, J=8.5 Hz); 7.05(2H, d,J=8.5 Hz); 66. i-Pr H H

Mol. Wt. = 467 Yield = 51% ¹H: 1.15(3H, t, J=6.9 Hz); 1.22(3H, t, J=7.1Hz); 1.31(6H, d, J=6 Hz); 2.90(2H, dd); 3.33–3.35(1H, m); 3.84(2H, t,J=6.6 Hz); 3.33–3.58(2H, m); 3.91–3.95(1H, dd); 4.12–4.19(2H, q, J=7.0Hz); 4.29(2H, t, J=6.6 Hz); 6.55(2H, d, J=8.6 Hz); 6.10(1H, d, J=3.5Hz); 5.98(1H, d, J=3.4 Hz); 7.0–7.1(4H, m); 7.3–7.38(2H, m) 67. i-Pr H

Mol. Wt. = 543 Yield = 48% ¹H: 1.1(3H, t, J=6.99 Hz); 1.2(3H, t, J=7.1Hz); 1.36(6H, d, J=7 Hz); 2.9(2H, d, J=6.29 Hz); 3.0–3.1(1H, m);3.3–3.58(2H, m); 3.8(2H, t, J=6.8 Hz); 3.9(2H, t, J=7 Hz); 4.1–4.2(3H,m); 6.2(1H, s); 6.5–7.3(13H, m). 68. i-Pr

Mol. Wt. = 662 Yield = 44% ¹H: 1.08(3H, t, J=7.0 Hz); 1.16(3H, t, J=7.0Hz); 1.49(6H d, J=7 Hz); 2.85(2H, dd); 3.26(1H, m); 3.5(2H, m) ,3.87(2H, t); 3.9(1H, t); 4.09(2H, q); 4.19(2H, t); 6.53(2H, d, J=8.5 Hz)6.79(1H, s); 6.90–7.18(15H, m) 69.

H H

Mol. Wt. = 501 Yield = 15% ¹H: 1.12(3H, t, J=7.0 Hz); 1.21(3H, t, J=7.0Hz); 2.88(2H, d, J=6.0 Hz); 3.3(1H, m); 3.6(1H, m); 3.61(2H, t); 3.9(1H,m); 4.1(2H, t, J=7.9 Hz); 4.37(2H, t, J=6.0 Hz); 6.26(2H, dd, J=3.3 Hz);6.9(2H, d, J=9.0 Hz); 7.1(2H, m); 7.41–7.49(9H, m). 70.

—COOEt H

Mol. Wt. = 573 Yield = 13.5% ¹H: 1.1–1.25(9H, m); 2.8(2H, d, J=6.3 Hz);3.3(1H, m); 3.6(1H, m); 3.61(2H, m); 3.9(1H, t); 4.1–4.21(6H, m);6.3(1H, s); 6.9(2H, d, J=9.0 Hz); 7.1(2H, m); 7.42–7.47(9H, m) 71. i-PrH H CH₃ Mol. Wt. = 387 Yield = 32.4% ¹H: 1.15(3H, t, J=6.9 Hz); 1.2(3H,t, J=6.9 Hz); 1.25(6H, d, J=6.7 Hz); 2.27(3H, s); 2.9–3.0(3H, m);3.3–3.63(2H, m); 3.96(1H, dd, ); 4.06(2H, t, J=6.9 Hz); 4.14–4.24(4H,m); 5.83(2H, s); 6.73(2H, d, J=8.5 Hz); 7.15(2H, d, J=8.5 Hz).

PREPARATION 10(S)-Ethyl[3-{4-[2-(5-methyl-2-quinolinyl)pyrrole-1-yl)ethoxy]phenyl}-2-ethoxypropanoate(Example 72)

A mixture of diketo compound (0.8 g), pivalic acid (0.06 g), amino ester(0.4 g) in toluene(20 ml.) was heated to reflux for 3 hours withcontinuous removal of water using a Dean-Stark apparatus. Later it wascooled to 20–25° C. and toluene was distilled at reduced pressure. Tothe residue was added D.M. water (20 ml) and crude product was extractedwith ethylacetate (2×30 ml), washed with water (2×30 ml) and saturatedbrine solution (30 ml.). Organic layer was dried over Na₂SO₄ to obtainbrown thick oil (0.32 g). The crude product was purified by columnchromatography using sillica gel (100–200) and ethyl acetate:PETether(1:9) as an eluent to afford yellowish thick oil (0.1 g).

In like manner to that described in preparation 10, the followingcompounds of general formula (I) were prepared.

TABLE 8 Ex. Substituents on the pyrrole ring in (I) No. R₁ R₂ R₃ R₄ 72.CH₃ H H

Mol. Wt. = 472 Yield = 35% ¹H: 1.14(3H, t, J=6.99Hz); 1.23(3H, t,J=7.14Hz); 2.4(3H, s); 2.89–2.92(2H, m); 3.28–3.38(1H, m); 3.52–3.6(1H,m); 3.9–3.95(1H, m); 4.14(2H, q, J₁=7.08Hz, J₂=7.08 Hz); 4.45(2H, t,J=5.76Hz); 5.02(2H, t, J=5.79Hz); 6.02(1H, d, J=3.72Hz); 6.75– 6.78(3H,m); 7.10(2H, d, J=8.6Hz); 7.4–7.7(4H, m); 7.89(1H, d, J=8.3Hz); 8.0(1H,d, J=8.7Hz) 73. CH₃ H H

Mol. Wt. = 422 Yield = 23% ¹H: 1.15(3H, t, J=6.99Hz); 1.23(3H, t,J=7.14Hz); 2.39(3H, s); 2.91(2H, d, J=7.44 Hz); 3.58–3.80(2H, m);3.93(1H, t, J=6.63Hz); 3.99(2H, t, J=6.12Hz); 4.12–4.20(2H, q,J₁=7.11Hz, J₂=7.11Hz); 4.38(2H, t, J=6.12Hz); 6.01(1H, d, J=3.45Hz);6.30(1H, d, J=3.54Hz); 6.63(2H, d, J=8.61Hz); 7.10(2H, d, J=8.55Hz);7.33(2H, d, J=6Hz); 8.58(2H, d, J=5.89Hz) 74. CH₃ H H

Mol. Wt. = 422 Yield = 21% ¹H: 1.15(3H, t, J=7Hz); 1.22(3H, t, J=6.9Hz);2.39(3H, s); 2.91(2H, d, J=7.02Hz); 3.32–3.57(2H, m); 3.94(1H, t,J=6.63Hz); 4.15(2H, q, J₁=7.14Hz, J₂=7.11Hz); 4.25 (2H, t, J=6.06Hz);4.81(2H, t, J=6.07Hz); 5.95(1H, d, J=3.21Hz); 6.53(1H, d, J= 3.63Hz);6.75(2H, d, J=8.49Hz); 7.02–7.08(1H, m); 7.10(2H, d, J=8.64); 7.51(1H,d, J=8.07Hz); 7.5–7.6(1H, m); 8.49–8.50(1H, m) 75. CH₃ H H

Mol. Wt. = 422 24% ¹H: 1.15(3H, t, J=7Hz); 1.23(3H, t, J=7.11Hz);2.38(3H, s); 2.91(2H, t, J=3.78Hz); 3.32–3.58(2H, m); 3.9–3.97(3H, m);4.16(2H, q, J₁=7.11Hz, J₂=7.11Hz); 4.29(2H, t, J= 6.15Hz); 6.0(1H, d,J=3.45Hz); 6.17(1H, d, J=3.48Hz); 6.62(2H, d, J=8.64Hz); 7.09(2H, d,J=8.58Hz); 7.32–7.34(1H, m); 7.71–7.74(1H, m); 8.53–8.55(1H, m); 8.68–8.69(1H, m)

PREPARATION 11 (R/S)Methyl-2-ethoxy-3[6-[2-[2-(4-methoxyphenyl)-5-methyl-pyrrol-1-yl]ethoxy]napthalen-2yl]propanoate(Example 76)

A mixture of (R/S)-ethyl 3-(4-hydroxynapthyl)-2-ethoxypropionate (1 g)and dry potassium carbonate (0.7 g) in dimethyl formamide (20 mL) wasstirred at 80° C. for 30 min. Compound. No. 79 (Table 5) (1.2 g) wasadded at 40° C. and stirring was continued at 80° C. for 24 h. Thereaction mixture was to 20° C.–25° C. and 20 mL water was added. Thereaction mixture was extracted with ethyl acetate (2×30 mL), washed withwater (2×30 mL), brine (30 mL) and was dried over sodium sulfate. Theorganic layer was evaporated under reduced pressure to obtain an oilyproduct. The crude oily product was chromatographed over silica gel(100–200 mesh) using ethyl acetate: petroleum ether (1:9) as an eluentto afford the title compound as a yellow oil (0.6 g, 31%).

TABLE 9 Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 76.CH₃ H H

Mol. Wt. = 487 Yield = 31% ¹H: 1.14(3H, t, J=7Hz)Hz; 2.4(3H, s);3.1–3.16(2H, m); 3.3–3.8(1H, m); 3.55–3.64(1H, m); 3.68(3H, s); 3.84(3H,s); 4.03–4.41(3H, m); 4.32(2H, t, J=6.6Hz); 5.96(1H, d, J= 3.36Hz);6.0(1H, d, J=3.39Hz); 6.8(1H, d, J=2.37Hz); 6.9–7.0(3H, m);7.33–7.38(3H, m); 7.52–7.64(3H, m)

PREPARATION 12 (S)-Methyl 3-{4-[2-(2-phenyl-5-methylpyrrol-1-yl)ethoxy]phenyl}-2-methoxypropanoate (Example 77)

Using a similar procedure to that described in preparation 7, (S)-methyl3-(4-hydroxyphenyl)-2-methoxypropanoate (3.3 g), and mesylate (compoundno. 74, table 5), (4.38 g), gave the titled compound (1.2 g,20%).

In the like manner to that described in above example, the correspondingpropoxy derivative (Example no. 78) was prepared using (S)-Propyl3-(4-hydroxyphenyl)-2-propoxy propionate and mesylate (given in theTable 5).

TABLE 10 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 77. CH₃ H H

R = CH₃ Mol. Wt. = 393 Yield = 20% ¹H: 2.37(3H; s); 2.9–3.0(2H, m);3.33(3H, s); 3.71(3H, m); 3.92(3H, t, J=6.96Hz); 4.29 (2H, t, J=6.6Hz);5.97(1H, d, J=3.36Hz); 6.11(1H, d, J=3.39Hz); 6.6(2H, d, J=8.67 Hz);7.05(2H, d, J=8.64Hz); 7.30–7.40(5H, m). 78. CH₃ H H

R = C₃H₇ Mol. Wt. = 449 Yield = 20% ¹H: 0.83(3H, t, J= 7.4Hz); 0.89(3H,t, J=7.4Hz); 1.53–1.63(4H, m); 2.37(3H, s)2.91(2H, d, J=5.54 Hz);3.20–3.48(2H, m); 3.92(3H, t, J=6.59Hz); 4.06(2H, t, J=6.67Hz); 4.28(2H,t, J= 7.4Hz); 5.97(1H, d, J=3.39Hz); 6.11(1H, d, J=3.4Hz); 6.59(2H, d,J=8.64Hz); 7.07(2H, d, J=8.63Hz); 7.25–7.4(5H, m).

PREPARATION NO. 13 Ethyl (E/Z)2-ethoxy-3-[4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl]prop-2-enoate(Example 79)

To a solution of triethyl 2-ethoxyphosphonoacetate (12.5 g) in dry THF(60 mL) was added slowly to a well-stirred ice-cold suspension of NaH(1.8 g, 60% dispersion in oil) in dry THF (60 mL) under N₂ atmosphere.The reaction mixture was stirred at 0° C. for 30 min. and4-[2-(5-methyl-2-phenylpyrrol-1-yl) ethoxy]benzaldehyde (compound no.134, table 6) (10.8 g) in dry THF (80 mL) was added. The mixture wasallowed to warm up to 20° C. to 25° C. and stirred for 3.5 hrs. Thesolvent was evaporated and the residue was diluted with water (150 mL)further the product was extracted with ethyl acetate (2×150 mL). Thecombined extract was washed with water (150 mL), brine (50 mL), and wasdried over sodium sulfate. The solvent was evaporated under reducedpressure to afford crude product. The crude product was chromatographedover silica gel using pet. ether:ether (9:1) as an eluent to afford Eand Z isomers, which were isolated by removing the of solvents.

TABLE 11 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ 79. CH₃ HH Phenyl Mol. Wt. = 419 Yield = 40% E/Z-isomer 80. CH₃ H H Phenyl Mol.Wt. = 419 Yield = 15% E-isomer ¹H: 1.13(3H, t, J=7.14Hz); 1.4(3H, t,J=6.9Hz); 2.3(3H, s); 3.86–3.95(4H, m); 4.13(2H, q, J=7.1Hz); 4.27–4.31(2H, t, J=6.6Hz); 5.96(1H, d, J=3.3Hz); 6.03(1H, s); 6.11(1H, d,J=3.3Hz); 6.5–6.6(2H, d, J=8.7Hz); 7.03–7.06 (2H, d, J=8.5Hz)7.32–7.34(1H, m); 7.35–7.41(4H, m). 81. CH₃ H H Phenyl Mol. Wt. = 419Yield = 15% Z-isomer ¹H: 1.33–1.38(6H, t, J=7.0Hz); 2.38(3H, s);3.92–3.99(4H, m); 4.24–4.33(4H, m); 5.98(1H, d, J=3.3Hz); 6.11(1H, d,J=3.3Hz); 6.63–6.6(2H, d, J=8.9Hz); 6.92(1H, s); 7.33(1H, m);7.36–7.41(4H, m); 7.64–7.67(2H, d, J=8.8Hz).

PREPARATION 14 (R/S) Methyl2-ethoxy-3[4-[2-[2-methyl-5-phenyl-1H-pyrrol-1-yl]ethoxy]phenyl]propanoate(Example 82)

Mixture of E/Z compounds (Example no. 80 and 81) obtained in preparation13 (7.1 g, 0.016 mole) and magnesium turnings (7.3 g, 0.3 mole) in drymethanol (70 mL) was stirred at 25° C. for 3.5 hrs. H₂O (150 mL) wasadded and pH of the reaction mixture was adjusted to 2–3 with 35%hydrochloric acid. The product was extracted in ethyl acetate (2×100 mL)combined extract was washed with H₂O (2×100 mL) brine (100 mL) and driedover Na₂SO₄. The extract was concentrated under reduced pressure. Thecrude product was chromatographed over silica gel using pet. ether:ether(9:1) as an eluent. The product obtained was racemic mixture but ethylester was converted to methyl ester.

Alternatively, the E and Z compound mixture is hydrogenated in thepresence of 10% Pd/C catalyst at 60 psi pressure to obtain the titlecompound.

TABLE 12 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ 82. CH₃ HH Phenyl Mol. Wt. = 407 Yield = 50% ¹H: 1.15(3H, t, J=7.0Hz); 2.37(3H,s); 2.90–2.92(2H, m); 3.32–3.34(1H, m); 3.55–3.57(1H, m); 3.69(3H, s);3.90–3.97(2H, m); 4.29(2H, t, J=6.5Hz); 5.9(1H, d, J=3.41Hz); 6.1(1H, d,J=3.4Hz); 6.59(2H, d, J=8.6Hz); 7.05(2H, d, J=8.5Hz); 7.26–7.41 5H, m).

PREPARATION 15(S)-3-{4-[2-(5-ethyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoicacid (Example 96)

A mixture of substituted ester (prepared in example 24) (1.3 g), sodiumhydroxide (0.24 g in 5 mL D.M. water) in methanol (10 mL) was stirred at20° C. to 25° C. for 10 h. Methanol was evaporated under reducedpressure. The residue was diluted with water (10 mL) and was acidifiedwith dilute hydrochloric acid. The product was extracted with ethylacetate (3×20 mL) and washed with water (2×30 mL), brine (30 mL) and wasdried over sodium sulfate to obtain an oily product (1.17 g, 96%). Thecrude product (3 g) was used in next step without purification.

In like manner to that described in Preparation 15 above followingcompounds of the formula (I) (given in Table 13) were prepared from theappropriately substituted pyrrole derivatives described elsewhere:

TABLE 13 (I)

Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴ 83. CH₃ HCH₃ H Mol. Wt. = 331 Yield = 88% ¹H: 0.96(3H, t, J=6.76Hz); 1.9(3H, s);2.13(3H, s); 2.78(2H, m); 3.3–3.6(2H, m); 4.05 (5H, m); 5.53(1H, s);6.43(1H, s) 6.75(2H, d, J=9.0Hz); 7.07(2H, d, J=9.0Hz). 84. C₂H₅ H H HMol. Wt. = 331 Yield = 10% ¹H: 1.16(3H, t, J=6.9Hz); 1.27(3H, t,J=3.51Hz); 2.51(2H, m); 2.62(2H, q); 3.44–3.46 (2H, m); 4.03(1H, dd,J₁=4.23Hz, J₂=4.5Hz); 4.13(2H, t, J=5.2Hz); 4.18(2H, t, J= 3.76Hz);5.91–5.92(1H, m) 6.10(1H, t, J=3.12Hz); 6.70(1H, d, J=2.01Hz); 6.77(2H,d, J=8.7Hz); 7.135(2H, d, J=8.64Hz). 85. CHO H H H Mol. Wt. = 331 Yield= 75% ¹H: 1.10(3H, t, J=7Hz); 2.8–4.0(5H, m); 4.16(2H, t, J=4.9Hz);4.65(2H, t, J=4.9Hz); 6.22(1H, dd); 6.7(2H, d, J=8.5Hz); 6.97(1H, dd);7.1–7.4(1H, m); 7.1(2H, d, J=8.5Hz); 9.49(1H, s). 86. COCH₃ H H H Mol.Wt. = 345 Yield = 10% ¹H: 0.87(3H, t, J=6.87Hz); 2.39(3H, s); 2.66(2H,dd, J=11.55Hz); 2.95–3.06(2H, m); 3.73(1H, t, J=4.5Hz); 4.09(2H, t,J=4.74Hz); 4.60(2H, t, J=4.89Hz); 6.08(1H, dd, J₁= 2.64Hz, J₂=2.64Hz);6.58(2H, d, J=8.37Hz); 6.92–6.99(2H, m); 7.00(2H, d, J=8.34 Hz). 87. CH₃H H CH₂CH₃ Mol. Wt. = 345 Yield = 54% ¹H: 1.16(3H, t, J=7Hz); 1.28(3H,t, J=7Hz); 2.28(3H, m); 2.55(2H, t, J=7.4Hz); 3.06 (2H, dd);3.4–3.62(2H, m); 4.0–4.16(5H, m); 5.8–5.84(2H, m); 6.75(2H, d,J=6.78Hz); 7.14(2H, d, J=6.78Hz). 88. CH₃ H H (CH₂)₂CH₃ Mol. Wt. = 423Yield = 66% ¹H: 1.02(3H, t, J=6.9Hz); 1.17(3H, t, J=6.9Hz); 1.7(2H,sextet); 2.28(3H, s); 2.55(2H, t, J=7.7Hz); 2.94(1H, dd); 3.4(1H, dd);3.4–3.62(2H, m); 4.0–4.2(5H, m); 5.8–5.84 (2H, m); 6.75(2H, d, J=8.5Hz);7.14(2H, d, J=8.5Hz). 89. CH₃ H H (CH₂)₃CH₃ Mol. Wt. = 373 Yield = 76%¹H: 0.95(3H, t, J=7.2Hz); 1.17(3H, t, J=7.0Hz); 1.4–1.5(2H, m);1.6–1.7(2H, m); 2.28(3H, s); 2.57(2H, t, J=7.7Hz); 2.95(1H, dd);3.07(1H, dd); 3.4–3.5(1H, m); 3.53– 3.62(1H, m); 4.0–4.2(5H, m);5.8–5.83(2H, m); 6.77(2H, d, J=8.5Hz); 7.15(2H, d, J= 8.5Hz). 90. CH₃ HH

Mol. Wt. = 393 Yield = 96% ¹H: 1.16(3H, t, J=6.9Hz); 2.37(3H, s);2.92–3.02(2H, dd, J₁=7Hz, J₂=4.2Hz); 3.41– 3.58(2H, m); 3.92(2H, t);3.98–4.01(1H, m); 4.1–4.3(2H, t, J=6.5Hz); 5.96(1H, d, J= 3.3Hz);6.1(1H, d, J=3.3Hz); 6.6(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.06–7.09(2H, d, J=8.6Hz); 7.2–7.4(5H, m). 91. CH₃ H

H Mol. Wt. = 393 Yield = 96% ¹H: 1.12(3H, t, J=6.9Hz); 2.37(3H, s);2.92–3.02(2H, dd, J₁=7Hz, J₂=4.2Hz); 3.41– 3.58(2H, m); 3.92(2H, t);3.98–4.01(1H, m); 4.1–4.3(2H, t, J=6.5Hz); 5.96(1H, d, J= 3.3Hz);6.1(1H, d, J=3.3Hz); 6.6(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.2–7.4(5H, m). 92. CH₃ H H

Mol. Wt. = 407 Yield = 75% ¹H: 1.02(3H, t, J=6.9Hz); 2.34(3H, s);2.36(3H, s); 2.74(1H, dd); 3.0(1H, dd); 3.19– 3.22(1H, m); 3.4–3.45(1H,m); 3.78–3.79(1H, m); 3.8(2H, t, J=6.4Hz); 4.25(2H, t, J= 6.4Hz);5.96(1H, d, J=3.36Hz); 6.07(1H, d, J=3.3Hz); 6.1(1H, d, J=8.5Hz);7.09(2H, d, J=8.5Hz); 7.19(2H, d, J=8.5Hz); 7.28(2H, d, J=8.5Hz). 93.CH₃ H H

Mol. Wt. = 407 Yield = 100% ¹H: 1.08(3H, t, J=6.99Hz); 2.33(3H, s);2.35(3H, s); 2.62(2H, m); 3.28–3.31(2H, m); 3.71(1h, m); 3.90(2H, t,J=6.05Hz); 4.3(2H, t, J=6.05Hz); 5.86(1H, d, J=3.36Hz); 5.96(1H, d,J=3.4Hz); 6.57(2H, d, J=8.6Hz); 7.09(2H, d, J=8.6Hz); 7.13–7.29(4H, m).94. CH₃ H H

Mol. Wt. = 407 Yield = 85% — 95. CH₃ H H

Mol. Wt. = 423 Yield = 62% ¹H: 1.077(3H, t, J=7Hz); 2.368(3H, s);2.93(3H, s); 2.94(1H, m); 3.35–3.5(2H, m); 3.78(1H, t, J=7.1Hz); 3.8(3H,m); 3.9(2H, t J=7Hz); 4.25(2H, t, J=7Hz); 5.9(1H, d, J=3.36Hz); 6.0(1H,d, J=3.36Hz); 6.64(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.31 (2H, d,J=6.78Hz). 96. CH₃ H H

Mol. Wt. = 472 Yield = 84% ¹H: 1.02(3H, t, J=6.9Hz); 2.353(3H, s);2.74(1H, dd); 2.95(1H, dd); 3.19–3.28(1H, m); 3.4–3.45(1H, m); 3.8(1H,dd); 3.9(2H, t, J=6.21Hz); 4.26(2H, t, J=6.2Hz); 5.9(1H, d, J=3Hz);6.1(1H, d, J=3.4Hz); 6.6(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz); 7.29(2H,d, J=8.5Hz); 7.5(2H, d, J=8.5Hz). 97. CH₃ H H

Mol. Wt. = 419 Yield = 77% ¹H: 1.02(3H, t, J=6.9Hz); 2.3(3H, s);2.7–2.8(1H, m); 2.96(1H, m); 3.1–3.2(1H, m); 3.4–3.5(1H, m);3.86–3.91(2H, t, J=6.3Hz); 4.2–4.24(2H, t, J=6.3Hz); 5.9(1H, d, J=3.3Hz); 6.05(1H, d, J=3.3Hz); 6.56–6.59(2H, d, J=8.6Hz); 7.05–7.09(4H,m); 7.28–7.37 (2H, m). 98. CH₃ H H

Mol. Wt. = 427.5 Yield = 37% — 99.

H CH₃ H Mol. Wt. = 393 Yield = 41% — 100. CH₃ H

Mol. Wt. = 469 Yield = 83% ¹H: 1.16(3H, t, J=7Hz); 2.41(3H, s); 2.9(1H,dd); 3.05(1H, dd); 3.4–3.6(2H, m); 3.9 (2H, t, J=6.5Hz); 4.03(1H, dd);4.16(2H, t, J=6.5Hz); 6.2(1H, s); 6.5–7.4(14H, m). 101. i-Pr H H i-PrMol. Wt. = 387 Yield = 50% ¹H: 1.19(3H, t, J=6.8Hz); 1.24–1.26(12H, d,J=6.7Hz); 2.92–2.99(4H, complex); 3.40 (1H, m); 3.6(1H, m); 4.03(3H,complex); 4.24(2H, t, J=Hz); 5.87(2H, s); 6.75–6.76(2H, d, J=8.8Hz);7.13–7.15(2H, d, J=8.6Hz). 102. i-Pr H H

Mol. Wt. = 443 Yield = 87% ¹H: 0.94(3H, t, J=7.29Hz); 1.22(6H, d,J=7.29Hz); 2.49–2.51(2H, dd, J=6.75Hz); 3.03– 3.08(2H, m); 3.45–3.53(2H,m); 3.82(2H, t, J=5.91Hz); 4.29(2H, t, J=5.92Hz); 5.85 (1H, d,J=3.51Hz); 5.95(1H, d, J=3Hz); 6.52(2H, d, J=8.58Hz); 7.01(2H, d, J=8.52Hz); 7.29–7.40(5H, m). 103. i-Pr

H

Mol. Wt. = 558 Yield = 50% ¹H: 1.18(3H, t, J=6.9Hz); 1.51–1.53(6H, d,J=7Hz); 2.9–3.1(2H, m); 3.5–3.6(3H, Complex); 3.92(2H, t, J=6.2Hz);4.05(1H, m); 4.3(2H, t, J=6.2Hz); 6.31(1H, s); 6.58– 6.60(2H, d,J=6.7Hz); 7.1(4H, m); 7.30–7.38(4H, m); 7.5(1H, s); 7.58–7.59(2H, d)104. SCH₃ H H H Mol. Wt. = 349 Yield = 93% ¹H: 1.18(3H, t, J=7Hz);2.29(3H, s); 2.5(2H, m); 2.9–3.1(2H, m); 3.4–3.6(2H, m); 4.0– 4.04(1H,m); 4.2(2H, t, J=5.6Hz); 4.42(2H, t, J=5.6Hz); 6.1(1H, t, J=3.2Hz); 6.38(1H, dd); 6.8(2H, d, J=8.5Hz); 6.95(1H, dd); 7.15(2H, d, J=8.5Hz). 105.C₂H₅ H H C₂H₅ Mol. Wt. = 359 Yield = 99% ¹H: 1.16(3H, t, J=6.8Hz);1.29(6H, t, J=7.4Hz); 2.65(4H, q, J=7.4Hz); 2.94–3.05(2H, m);3.39–3.49(1H, m); 3.51–3.6(1H, m); 4.01–4.07(3H, m); 4.15(2H, t,J=5.8Hz); 5.86 (2H, s); 6.7(2H, d, 8.5Hz); 7.15(2H, d, J=8.5Hz) 106.C₂H₅ H H C₆H₅ Mol. Wt. = 407 Yield = 90% ¹H: 1.16(3H, t, J=6.99Hz);1.34(3H, t, J=7.4Hz); 2.73–2.78(2H, q, J=7.5Hz,); 2.9–3.9 (2H, m);3.4–3.48(1H, m); 3.52–3.6(1H, m); 3.9(2H, t, J=6.63Hz); 4.0–4.05(1H, m);4.3 (2H, t, 6.75Hz); 6.0(1H, d, J=3.48Hz); 6.15(1H, d, J=3.5Hz); 6.6(2H,d, J=8.5Hz); 7.08 (2H, d, J=8.6Hz); 7.3–7.4(5H, m) 107. CH₃ H H

Mol. Wt. = 421 Yield = 98% ¹H: 1.16(3H, t, J=6.9Hz); 2.29(3H, s);2.88–3.04(6H, m); 3.38–3.48(1H, m); 3.53–3.62 (1H, m); 3.99–4.07(3H, m);4.15(2H, t, J=7Hz); 5.85(1H, d, J=3.3Hz); 5.9(1H, d, J=3.3 Hz); 6.7(2H,d, J=8.6Hz); 7.14(2H, d, J=8.6Hz); 7.2–7.3(5H, m) 108. CH₃ H H

Mol. Wt. = 423 Yield = 90% ¹H: 1.15(3H, t, J=6.9Hz); 2.24(3H, s);2.89–2.95(2H, m); 3.3–3.58(2H, m); 3.67(3H, s); 3.78–4.17(3H, m);4.28(2H, t, J=6Hz); 5.89(1H, d, J=3.1Hz); 6.06(1H, d, J=3Hz);6.49–7.21(8H, m) 109. CH₃ H H

Mol. Wt. = 399 Yield = 92% ¹H: 1.17(3H, t, J=6.9Hz); 1.3–1.4(6H, m);1.75–2.5(5H, m); 2.27(3H, s); 2.9–3.08(2H, m); 3.38–3.45(1H, m);3.57–3.65(1H, m); 3.98–4.15(3H, m); 4.2(2H, t, J=7.2Hz); 5.8(1H, d,J=3.4Hz); 5.84(1H, d, J=3.3Hz); 6.78(2H, d, J=8.5Hz); 7.17(2H, d,J=8.5Hz) 110. CH₃ H H

Mol. Wt. = 469 Yield = 85% ¹H: 1.16(3H, t, J=6.9Hz); 2.33(3H, s);2.9–3.0(2H, m); 3.38–3.48(1H, m); 3.55–3.66(1H, m); 3.88–3.94(1H, m);3.99(2H, t, J=5.8Hz); 4.3(2H, t, J=6.3Hz); 5.91(1H, d, J=3.3Hz);6.07(1H, d, J=3.4Hz); 6.63(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz);7.3–7.5(5H, m); 7.68 (4H, d, J=8.2Hz) 111. CH₃ H H

Mol. Wt. = 383 Yield = 92% ¹H: 1.16(3H, t, J=6.99Hz); 2.32(3H, s);2.9–3.0(2H, m); 3.38–3.48(1H, m); 3.55–3.64 (1H, m); 4.00–4.04(1H, dd,J=4.2Hz); 4.15(2H, t, J=5.98Hz); 4.38(2H, t, J=6.1Hz); 5.9 (1H, d,J=3.48Hz); 6.32(1H, d, J=3.55Hz); 6.35(1H, d, J=3.5Hz); 6.42–6.43(1H,m); 6.7 (2H, d, J=8.5Hz); 7.14(2H, d, J=8.5Hz); 7.4–7.41(1H, m) 112. CH₃H H

Mol. Wt. = 439 Yield = 99% ¹H: 1.14(3H, t, J=6.9Hz); 2.37(3H, s);2.48(3H, s); 2.92–3.06(2H, m); 3.32–3.42(1H, m); 3.57–3.64(1H, m);3.9(2H, t, J=6.36Hz); 4.0(1H, dd); 4.28(2H, t, J=6.z); 5.9(1H, d, J=3.3Hz); 6.08(1H, d, J=3.38Hz); z); 6.6(2H, d, J=8.5, Hz); 7.1(2H, d,J=8.5Hz); 7.26(2H, d, J= 8.4Hz); 7.3(2H, d, J=8.34Hz) 113. CH₃ H H

Mol. Wt. = 397 Yield = 95% ¹H: 1.07(3H, t, J=6.97Hz); 2.27(3H, s);2.3(3H, s); 2.7–2.8(1H, m); 2.89–2.96(1H, m); 3.2–3.3(1H, m);3.5–3.6(1H, m); 3.76–3.8(1H, m); 4.12(2H, t, J=5.8Hz); 4.35(2H, t, J=5.9Hz); 5.79–5.81(1H, dd, J=0.69Hz, J=0.69Hz); 6.01–6.02(1H, dd, J=1, 1Hz);6.15(1H, d, J=3.5Hz); 6.2(1H, d, J=3.1Hz); 6.7(2H, d, 8.6)Hz; 7.14(2H,d, J=8.6Hz) (solvent used is CD₃OD) 114. CH₃ H H

Mol. Wt. = 418 Yield = 85% ¹H: 1.069(3H, t, J=6.9Hz); 2.34(3H, s);2.74–2.8(2H, m); 3.2–3.25(1H, m); 3.5–3.58(1H, m); 3.76–3.8(1H, dd);3.93(2H, t, J=5.58Hz); 4.37(2H, t, J=5.56Hz); 5.9(1H, d, J=3.3 Hz);6.16(1H, d, J=3.5Hz); 6.57(2H, d, J=8.5Hz); 7.1(2H, d, J=8.5Hz);7.56(2H, d, J=8.57Hz); 7.68(2H, d, J=8.59Hz) (solvent used is CD₃OD)115. CH₃ H H

Mol. Wt. = 485 Yield = 92% ¹H: 1.07(3H, t, J=6.96Hz); 2.33(3H, s);2.7–2.95(2H, m); 3.2–3.35(1H, m); 3.5–3.6(1H, m); 3.76–3.8(1H, m);3.94(2H, t, J=5.9Hz); 4.28(2H, t, J=5.9Hz); 5.86(1H, d, J=3.1Hz);5.96(1H, d, J=3.4Hz); 6.6(2H, d, J=8.5Hz); 7.08–7.37(11H, m) (solventused is CD₃OD) 116. CH₃ H H

Mol. Wt. = 535 Yield = 80% ¹H: 1.07(3H, t, J=6.96Hz); 2.26(3H, s);2.37(3H, s); 2.7–2.95(2H, m); 3.17–3.3(1H, m); 3.5–3.6(1H, m);3.6–3.8(5H, m); 5.7(1H, d, J=3.48Hz); 5.8(1H, d, J=2.79Hz); 6.25–6.27(1H, m); 6.34(1H, t, J=3.36Hz); 6.6(2H, d, J=8.5Hz); 7.12(2H, d,J=8.5Hz); 7.25(2H, d, J=8.1Hz); 7.35(2H, d, J=8.4Hz); 7.5–7.51(1H, m)(solvent used is CD₃OD) 117. CH₃ H H

Mol. Wt. = 453 Yield = 88% ¹H: 1.07(3H, t, J=6.9Hz); 2.32(3H, s);2.7–2.93(2H, m); 3.2–3.3(1H, m); 3.5–3.6(1H, m); 3.78(3H, s); 3.84(3H,s); 3.9(2H, t, J=6Hz); 3.93–3.95(1H, m); 4.2(2H, t, J=6Hz); 5.84 (1H, d,J=3.1Hz); 6.0(1H, d, J=3.1Hz); 6.59(2H, d, J=8.5Hz); 6.92–7.0(3H, m);7.07(2H, d, J=8.57Hz) (solvent used is CD₃OD) 118. CH₃ H H

Mol. Wt. = 455 Yield = 88% ¹H: 1.19(3H, t, J=6.9Hz); 2.38(3H, s);2.8(3H, s); 2.9–3.06(2H, m); 3.43–3.52(1H, m); 3.62–3.72(1H, m);4.0–4.12(3H, m); 4.23(2H, t, J=3.8Hz); 6.0(1H, d, J=3.2Hz); 6.18(1H, d,J=3.2Hz); 6.52–6.55(2H, dd, J=6.4Hz); 7.02–7.07(2H, dd, J=6.3Hz);7.49–7.5(2H, dd, J=3.2Hz); 7.6–7.63(2H, dd, J=3.69Hz) 119. CH₃ H H

Mol. Wt. = 450 Yield = 99% ¹H: 1.09(3H, t, J=6.99Hz); 2.13(3H, s);2.32(3H, s); 2.77–2.98(2H, m); 3.25–3.36(1H, m); 3.5–3.6(1H, m);3.90(2H, t, J=6.18Hz); 3.92–3.94(1H, m); 4.27(2H, t, J=6.0Hz); 5.85(1H,d, J=3.0Hz); 5.96(1H, d, J=3.3Hz); 6.58(2H, d, J=8.6Hz); 7.06(2H, d,J=8.6 Hz); 7.3(2H, d, J=8.6Hz); 7.57(2H, d, J=8.6Hz) 120. CH₃ H H

Mol. Wt. = 520 Yield = 80% ¹H: 1.15(3H, s, J=6.9Hz); 1.25–2.1(6H, m);2.3(3H, s); 2.9–3.03(2H, m); 3.2–3.33(1H, m); 3.22–3.6(5H, m);3.58–3.66(1H, m); 3.9(2H, t, J=6.9Hz); 3.98(2H, t, J=6.9Hz); 4.15 (2H,t, J=6Hz); 4.57(2H, t, J=4.87Hz); 5.9(1H, d, J=3.1Hz); 6.0(1H, d,J=3.3Hz); 6.45(2H, d, J=8.5Hz); 6.96(2H, d, J=8.6Hz); 7.0(2H, d,J=8.5Hz); 7.3(2H, d, J=8.5Hz) 121. CH₃ H H

Mol. Wt. = 449 Yield = 97% ¹H: 1.07(3H, t, J=6.9Hz); 2.3(3H, s);2.9–3.2(2H, m); 3.2–3.8(3H, m); 3.9(2H, t, J=6.03 Hz); 4.2(2H, t,J=6.2Hz); 4.55(2H, d, J=1.5Hz); 5.12–5.3(1H, dd); 5.43–5.44(1H, dd,J=1.67Hz); 5.83(1H, d, J=3.3Hz); 5.9(1H, d, J=3.2Hz); 6.0–6.12(1H, m);6.58(2H, d, J= 8.5Hz); 6.96(2H, d, J=8.6Hz); 7.1(2H, d, J=8.5Hz);7.28(2H, d, J=8.7Hz) (solvent used is CD₃OD) 122. CH₃ H H

Mol. Wt. = 501 Yield = 94% ¹H: 1.07(3H, t, J=6.97Hz); 2.3(3H, s);2.7–2.8(1H, m) 2.88–2.95(1H, m); 3.2–3.33(1H, m); 3.5–3.6(1H, m);3.73–3.8(1H, m); 3.92(2H, t, J=5.8Hz); 4.3(2H, t, J=5.9Hz); 5.87 (1H, d,J=3.4Hz); 6.0(1H, d, J=3.4Hz); 6.57(2H, d, J=8.5Hz); 7.1(2H, d,J=8.6Hz); 7.26– 7.35(9H, m) (solvent used is CD₃OD) 123. CH₃ H H

Mol. Wt. = 517 Yield = 90% ¹H: 1.07(3H, t, J=6.98Hz); 2.3(3H, s);2.7–2.94(2H, m); 3.2–3.34(1H, m); 3.5–3.6(1H, m); 3.74–3.8(1H, m);3.9(2H, t, J=5.87Hz); 4.30(2H, t, J=5.87Hz); 5.87(1H, d, J=3.45 Hz);6.1(1H, d, J=3.45Hz); 6.56(2H, d, J=8.56Hz); 7.17(2H, d, J=8.54Hz);7.51–7.56 (5H, m); 7.65–7.77(4H, m) (solvent used is CD₃OD) 124. CH₃ H H

Mol. Wt. = 471 Yield = 80% ¹H: 1.26(3H, t, J=6.2Hz); 2.39(3H, s);2.97–3.09(2H, m); 3.09(3H, s); 3.4–3.5(1H, m); 3.55–3.64(1H, m); 4.0(2H,t, 6.0Hz); 4.02–4.06(1H, m); 4.33(2H, t, J=6.12Hz); 6.02(1H, d,J=3.3Hz); 6.24(1H, d, J=3.5Hz); 6.6(2H, d, J=8.58Hz); 7.11(2H, d,J=8.58Hz); 7.6 (2H, d, J=8.4)Hz; 7.93(2H, d, J=8.4Hz) 125. CH₃ H H

Mol. Wt. = 505 Yield = 94% ¹H: 0.88–1.86(14H, m); 2.29(3H, s);2.52–3.4(4H, m); 3.75(2H, d, J=3.39Hz); 3.76–4.18 (5H, m); 5.9(1H, d,J=2.97Hz); 6.01(1H, d, 3.3Hz); 6.5(2H, d, J=8.0Hz); 6.8(2H, d, J=8.6Hz); 7.0(2H, d, J=8.0Hz); 7.26(2H, d, J=8.5Hz) 126. COPh H H H Mol. Wt.= 407.2 Yield = 76% ¹H: 1.15(3H, t, J=6.96Hz); 2.84–2.95(2H, m);3.33–3.42(1H, m); 3.48–3.58(1H, m); 3.98– 4.13(5H, m); 5.64–5.66(1H, dd,J₁=1.5Hz, J₂=1.5Hz); 6.17(1H, , d, J=3.4Hz); 6.64–6.72 (1H, dd,J₁=1.65Hz, J₂=1.65Hz); 6.7–7.9(9H, m) 127. CH₃ H H

Mol. Wt. = 394 Yield = 36% ¹H: 1.07(3H, t, J=6.99Hz); 2.35(3H, s);2.75–2.89(2H, m); 3.22–3.28(1H, m); 3.57–3.76 (2H, m); 3.96(2H, t,J=5.5Hz); 4.32(2H, t, J=5.5Hz); 5.9(1H, d, J=3.45Hz); 6.12(1H, d,J=3.49Hz); 6.55(2H, d, J=8.6Hz); 7.08(2H, d, J=8.6Hz); 7.42–7.45(1H, m);7.85–7.88 (1H, m); 8.4–8.42(1H, m); 8.55(1H, s) 128. CH₃ H H

Mol. Wt. = 357 Yield = 58% ¹H: 0.6–0.62(2H, m); 0.81–0.84(2H, m);1.3(3H, t, J=6.99Hz); 1.3–1.8(1H, m); 2.28(3H, s); 2.97–3.04(2H, m);3.4–3.6(2H, m); 4.02–4.03(1H, m); 4.15(2H, t, J=7.9Hz); 4.33(2H, t,J=6.38Hz); 5.7(1H, d, J=3.3Hz); 5.76(1H, d, J=3.28Hz); 6.78(2H, d,J=8.6Hz); 7.15(2H, d, J=8.57Hz) 129. CH₃ H H

Mol. Wt. = 433 Yield = 29% ¹H: 1.06(3H, t, J=6.99Hz); 2.37(3H, s);2.60–2.68(2H, m); 3.2–3.6(2H, m); 3.7–3.8(1H, m); 4.22(2H, t, J=5.5Hz);4.55(2H, t, J=5.63Hz); 5.93(1H, d, J=3.63Hz); 6.52(1H, d, J=3.62Hz);6.69(2H, d, J=8.57Hz); 6.76(1H, s); 7.1(2H, d, J=8.55Hz); 7.18–7.54 (4H,m) 130. CH₃ COOCH₃ H

Mol. Wt. = 451 Yield = 46% ¹H: 1.08(3H, t, J=6.98Hz); 2.66(3H, s);2.88–2.89(2H, m); 3.22–3.31(3H, m); 3.77(3H, s); 3.93(2H, t, J=5.64Hz);4.37(2H, t, J=5.64Hz); 6.45(1H, s); 6.59(2H, d, J=8.6Hz); 7.11(2H, d,J=8.58v); 7.36–7.45(5H, m) 131. CH₃ COOH H

Mol. Wt. = 437 Yield = 58% ¹H: 1.2(3H, t, J=6.99Hz); 2.68(3H, s);2.93–3.03(2H, m); 3.43–3.49(2H, m); 3.89(2H, t, J=5.74Hz); 4.04(1H, t,J=5.88Hz); 4.31(2H, t, J=5.75Hz); 6.58–6.61(3H, m); 7.09 (2H, d,J=8.58Hz); 7.37–7.45(5H, m) 132. CH₃ H H

Mol. Wt. = 437 Yield = 82% ¹H: 1.07(3H, t, J=6.99Hz); 2.32(3H, s);2.6–2.63(2H, m); 3.23–3.31(2H, m); 3.32–3.8 (1H, m); 3.92(2H, t,J=5.98Hz); 4.26(2H, t, J=5.97Hz); 5.83(1H, d, J=3.36Hz); 5.91 (1H, d,J=3.39Hz); 5.98(2H, s); 6.6(2H, d, J=8.64Hz); 6.84–6.88(3H, m); 7.11(2H,d, J= 8.58Hz) 133. CH₃ H H

Mol. Wt. = 443 Yield = 82% ¹H: 1.06(3H, t, J=6.97Hz); 2.4(3H, s);2.6–2.62(2H, m); 3.21–3.31(2H, m); 3.71(2H, t, J= 6.04Hz); 3.8–4.0(3H,m); 5.99(1H, d, J=3.35Hz); 6.03(1H, d, J=3.36Hz); 6.35(2H, d, J=8.64Hz);6.99(2H, d, J=8.61Hz); 7.4–7.92(7H, m) 134. CH₃ H H

Mol. Wt. = 499 Yield = 93% ¹H: 1.07(3H, t, J=6.97Hz); 2.33(3H, s);2.64–3.2(2H, m); 3.28–3.33(3H, m); 3.9(2H, t, J= 5.88Hz); 4.25(2H, t,J=5.88Hz); 5.11(2H, s); 5.86(1H, d, J=3.78Hz); 6.01(1H, d, J= 3.39Hz);6.58(2H, d, J=8.61Hz); 6.69–7.01(3H, m); 7.1(2H, d, J=8.58Hz); 7.28–7.43(6H, m) 135. CH₃ H H

Mol. Wt. = 478 Yield = 79% ¹H: 1.08(3H, t, J=6.97Hz); 2.33(3H, s);2.6–2.62(2H, m); 3.26–4(3H, m); 4.06(2H, t, J= 5.73Hz); 4.34(2H, t,J=5.7Hz); 5.86(1H, d, J=3.51Hz); 6.12(1H, d, J=3.54Hz); 6.67(2H, d,J=8.64Hz); 6.86(1H, d, J=3.81Hz); 7.05(1H, d, J=3.87Hz); 7.13(2H, d, J=8.58Hz) 136. CH₃ H H

Mol. Wt. = 394 Yield = 20% ¹H: 1.08(3H, t, J=6.91Hz); 2.37(3H, s);2.7–3.1(2H, m); 3.23–4.0(3H, m); 4.17(2H, t, J= 5.64Hz); 4.71–4.78(2H,m); 5.92(1H, d, J=3.66Hz); 6.49(1H, d, J=3.69Hz); 6.67 (2H, d,J=8.52Hz); 7.10–7.14(3H, m); 7.58(1H, d, J=8.1Hz); 7.69–7.72(1H, m);8.47– 8.49(1H, m) 137. CH₃ H H

Mol. Wt. = 394 Yield = 20% ¹H: (3H, t, J=6Hz); 2.38(3H, s); 3.01(2H, m);3.51–3.67(2H, m); 4.02–4.13(3H, m); 4.37 (2H, t, J=6Hz); 6.05(1H, d,J=3.45Hz); 6.34(1H, d, J=3.57Hz); 6.49(2H, d, J=8.55 Hz); 7.04(2H, d,J=8.55Hz); 7.30(2H, d, J=6.27Hz); 8.44(2H, d, J=6.12Hz) 138. CH₃ H H

Mol. Wt. = 451 Yield = 87% ¹H: 1.07(3H, t, J=6.67Hz); 1.32(6H, d,J=6Hz); 2.32(3H, s); 2.61–2.62(2H, m); 3.28– 3.32(1H, m); 3.33–3.83(2H,m); 3.91(2H, t, J=6.03Hz); 4.25(2H, t, J=6.03Hz); 4.62 (1H, t,J=6.06Hz); 5.83(1H, d, J=3.39Hz); 5.91(1H, d, J=3.39Hz); 6.59(2H, d, J=8.37Hz); 6.92(2H, d, J=8.7Hz); 7.10(2H, d, J=8.43Hz); 7.27(2H, d,J=8.73Hz) 139. CH₃ H CH₃

Mol. Wt. = 407 Yield = 87% ¹H: 1.1(3H, t, J=6.29Hz); 2.2(3H, s);2.61(3H, s); 2.87(2H, d, d, 2H); 3.22–3.28(2H, m); 3.75–3.82(1H, m);3.8(2H, t, J=6.16Hz); 4.14(2H, t, J=6.16Hz); 5.73(1H, s); 6.5 (2H, d,J=8.5Hz); 7.08(2H, d, J=8.5Hz); 7.26–7.44(5H, m) 140. CH₃ H H

Mol. Wt. = 399 Yield = 55% ¹H: 1.08(3H, t, J=6.9Hz); 2.3(3H, s);2.88(2H, m); 3.22–3.6(2H, m); 3.8(1H, m); 4.02 (2H, t, J=6.0Hz); 4.3(2H,t, J=6.0Hz); 5.8(1H, d, J=3.5Hz); 6.1(1H, d, J=3.5Hz); 6.6(2H, d,J=8.6Hz); 7.04–7.1(2H, m); 7.13–7.15(2H, m); 7.32–7.34(1H, m) (solventused is CD₃OD) 141. CH₃ H H

Mol. Wt. = 499 Yield = 78% ¹H: 1.07(3H, t, J=6.9Hz); 2.3(3H, s);2.7–2.9(2H, m); 3.4–3.5(2H, m); 3.7–3.8(1H, m); 3.9(2H, m); 4.2(2H, m);5.0(2H, s), 5.8(1H, d, J=3.4Hz); 5.9(1H, d, J=3.3Hz); 6.5(2H, d,J=8.7Hz); 7.0(2H, d, J=8.5Hz); 7.2(2H, d, J=8.8Hz); 7.35–7.44(7H, m)(solvent used is CD₃OD) 142. CH₃ H H

Mol. Wt. = 409 Yield = 88% ¹H: 1.2(3H, t, J=7Hz); 2.3(3H, s); 3.0(2H,m); 3.5(2H, m); 3.9(2H, m); 4.1(1H, m); 4.2 (2H, m); 5.9(1H, d,J=3.3Hz); 6.0(1H, d, J=3.3Hz); 6.5(2H, d, J=8.6Hz); 6.86(2H, d,J=8.6Hz); 7.0(2H, d, J=8.7Hz); 7.22–7.26(2H, m) 143. H H H Ph Mol. Wt. =379 Yield = 73% ¹H: 1.08(3H, t, J=6.99Hz); 2.7–2.9(2H, m); 3.1–3.2(1H,m); 3.4–3.5(1H, m); 3.7(1H, m); 4.06(2H, t, J=5.6Hz); 4.29(2H, t,J=5.6Hz); 6.08(2H, m); 6.6(2H, d, J=8.6Hz); 6.8(1H, m); 7.1(2H, d,J=8.6Hz); 7.38–7.39(5H, m) (solvent used is CD₃OD) 144. CH₃ H H

Mol. Wt. = 433 Yield = 90% ¹H: 1.08(3H, t, J=6.9Hz); 2.3(3H, s);2.75–3.0(2H, m); 3.2–3.3(1H, m); 3.5–3.6(1H, m); 3.8(1H, m); 4.05(2H, t,J=5.6Hz); 4.31(2H, t, J=5.6Hz); 5.8(1H, d, J=3.4Hz); 6.1 (1H, d,J=3.5Hz); 6.6(2H, d, J=8.6Hz); 6.8(1H, d, J=3.8Hz); 6.9(1H, d, J=3.8Hz);7.1(2H, d, J=8.6Hz) (solvent used is CD₃OD) 145. CH₃ H H

Mol. Wt. = 437 Yield = 77% ¹H: 1.07(3H, t, J=6.98Hz); 1.39(3H, t,J=6.96Hz); 2.31(3H, s); 2.88(2H, m); 3.29(1H, m); 3.6(1H, m); 3.78(1H,m); 3.88(2H, t, J=6.03Hz); 4.04(2H, q, J=6.97Hz); 4.23 (2H, t,J=6.12Hz); 5.82(1H, d, J=3.36Hz); 5.9(1H, d, J=3.37Hz); 6.7(2H, d,J=8.61 Hz); 6.91(2H, d, J=6.93Hz); 7.8(2H, d, J=8.58)Hz; 7.25(2H, d,J=6.67Hz) 146. CH₃ H H

Mol. Wt. = 399 Yield = 97% ¹H: 1.08(3H, t, J=6.9Hz), 2.3(3H, s);2.45(3H, s); 2.89(2H, m); 3.23–3.57(2H, m); 3.6– 3.9(1H, m); 4.0(2H, t,J=6Hz); 4.3(2H, t, J=6Hz); 5.8(1H, d, J=3.3Hz); 6.0(1H, d, J= 3.47Hz);6.65(2H, d, J=8.6Hz); 6.69–6.71(1H, m); 6.79(1H, d, J=3.44); 7.11(2H, d,J= 8.6Hz) (solvent used is CD₃OD) 147. CH₃ CH₃ H C₆H₅ Mol. Wt. = 407Yield = 50% ¹H: 1.0(3H, t, J=7Hz); 2.1(3H, s); 2.23(3H, s); 2.7–2.9(2H,m); 3.55(1H, m); 3.56(1H, m), 3.75(1H, m); 3.9(2H, t, J=6.1Hz); 4.2(2H,t,); 5.87(1H, s); 6.5(2H, d, J=8.5Hz); 7.0(2H, d, J=8.5Hz); 7.2–7.3(3H,m); 7.3–7.36(2H, m) (solvent used is CD₃OD) 148. CH₃ H H

Mol. Wt. = 487 Yield = 50% ¹H: 0.9(3H, t, J=6.9Hz); 2.6(3H, s);2.7–2.8(1H, m), 2.9–3.0(1H, m); 3.0–3.1(4H, m); 3.3–3.4(1H, m);3.7–3.8(1H, m); 3.8–3.9(2H, m); 4.1–4.2(2H, m); 5.9(1H, d, J=3.3Hz);6.0(1H, d, J=3.4Hz); 6.4(2H, d, J=8.4Hz); 6.9(2H, d, J=8.47Hz);7.2–7.3(2H, m); 7.38(2H, d, J=8.6Hz) 149. H H H H Mol. Wt. = 303 Yield =79% ¹H: 1.16(3H, t, J=6.9Hz); 2.97(1H, dd); 3.0(1H, dd); 3.36–3.6(2H,m); 4.01(1H, dd); 4.17–4.28(4H, m) 6.16(2H, t, J=2.1Hz); 6.75–6.80(4H,m); 6.7(2H, t, J=2.1Hz); 6.8 (2H, d, J=8.5Hz); 7.15(2H, d, J=8.5Hz).150. CH₃ H H CH₃ Mol. Wt. = 331.2 Yield = 59% ¹H: 1.18(3H, t, J=7Hz);2.28(6H, s); 2.93–3.08(2H, m); 3.45–3.59(2H, m); 4.03–4.18 (5H, m);5.79(1H, s); 6.0(1H, s); 6.78(2H, d, J=8.5Hz); 7.15(2H, d, J=8.5Hz).151. i-Pr

H i-Pr Mol. Wt. = 463 Yield = 48% ¹H: 1.12(3H, t, J=6.9Hz); 1.2–1.3(12H,m); 2.96–3.76(7H, m); 4.03–4.05(2H, m); 4.30 (2H, t, J=6.9Hz); 5.89(1H,s); 6.80(2H, d, J=8.5Hz); 7.15(2H, d, J=8.5Hz); 7.2–7.33 (5H, m). 152.i-Pr H H

Mol. Wt. = 451 Yield = 84% ¹H: 1.2(3H, t, J=7Hz); 1.29(6H, d, J=6Hz);2.90(2H, dd); 3.04–3.06(1H, m); 3.33– 3.59(2H, m); 3.8(3H, s); 4.0(1H,t); 3.84(2H, t, J=6Hz); 4.28(2H, t, J=6.7Hz); 5.98 (1H, d, J=3.4Hz);6.56(2H, d, J=8.6Hz); 6.08(1H, d, J=3.5Hz); 6.93(2H, d, J= 8.7Hz);7.03(2H, t, J=8.5Hz); 7.32(2H, d, J=8.5Hz). 153. i-Pr H H

Mol. Wt. = 439 Yield = 36% ¹H: 1.17(3H, t, J=6.9Hz); 1.31(6H, d,J=6.9Hz); 2.93(2H, dd); 3.03–3.1(1H, m); 3.33– 3.58(2H, m); 3.84(2H, t,J=6.5Hz); 4.0(1H, m); 4.29(2H, t, J=6.6Hz); 6.56(2H, d, J= 8.6Hz);6.10(1H, d, J=3.5Hz); 6.00(1H, d, J=3.5Hz); 7.0–7.1(4H, m); 7.3–7.38(2H,m). 154. i-Pr H

Mol. Wt. = 515 Yield = 53% ¹H: 1.19(3H, t, J=6.9Hz); 1.36(6H, d, J=7Hz);2.95(2H, dd, J=7.1Hz); 3.0–3.1(1H, m); 3.45–3.57(2H, m); 3.83(2H, t,J=6.5Hz); 4.0–4.04(1H, m); 4.2(2H, t, J=6.7Hz); 6.2 (1H, s);6.5–7.28(13H, m). 155. i-Pr

Mol. Wt. = 634 Yield = 61% ¹H: 0.91(3H, t, J=6.7Hz); 1.45(6H, d,J=6.8Hz); 2.91(2H, dd); 3.13(1H, m); 3.32–3.49 (2H, m); 3.80(3H, m)4.15(2H, t, J=6.5Hz); 6.46(2H, d); 6.78(1H, s); 6.86–7.18(15H, m). 156.

—H H

Mol. Wt. = 473 Yield = 60.3% ¹H: 0.9(3H, t); 2.6(1H, t); 2.9(2H, d);3.2(1H, m); 3.5(2H, t); 3.6(1H, m); 6.21(2H, dd, J=3Hz); 6.9(2H, d);7.0(2H, t, J=9.0Hz); 7.31–7.6(9H, m). 157.

—COOEt H

Mol. Wt. = 545 Yield = 83% ¹H: 0.9(3H, t); 2.6(1H, t); 2.9(2H, d);3.2(1H, m); 3.5(2H, t); 3.6(1H, m); 6.7(1H, s); 6.9 (2H, d); 7.1(2H, t);7.29–7.6(9H, m). 158. i-Pr H H CH₃ Mol. Wt. = 359 Yield = 20% ¹H:1.17(3H, t, J=6.9Hz); 1.26(6H, d, J=6.7Hz); 2.27(3H, s); 2.9–3.0(1H, m);3.07 (2H, dd); 3.42–3.58(2H, m); 4.02–4.08(3H, m); 4.2(2H, t, J=6.3Hz);5.83(2H, s); 6.7 (2H, d, J=8Hz); 7.15(2H, d, J=8Hz).

PREPARATION 16 (R/S)2-ethoxy-3[6-[2-[2-(4-methoxyphenyl)-5-methyl-pyrrol-1-yl]ethoxy]napthalen-2yl]propanoic acid

In a like manner to the procedure given in Preparation 15, the estersdescribed in examples 76 can be converted to a corresponding acid.

TABLE 14 Ex. Substituents on the pyrrole ring in (I) No. R¹ R² R³ R⁴159. CH₃ H H

Mol. Wt. = 473 Yield = 82% ¹H: 1.15(3H, t, J=7Hz); 2.4(3H, s);3.1–3.16(2H, m); 3.4–3.62(2H, m); 3.57(3H, s); 4.07 (2H, t, J=6.6Hz);4.13–4.18(1H, dd, J=3.48Hz); 4.32(2H, t, J=6.6Hz); 5.96(1H, d, J=3.36Hz); 6.0(1H, d, J=3.39Hz); 6.8(1H, d, J=2.37Hz); 6.9–7.0(3H, m);7.33–7.38(3H, m); 7.52–7.64(3H, m)

PREPARATION 17 (E/Z)3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropen-2-oicacid (Example 161)

In a like manner to the procedure given in Preparation 15, the estersdescribed in examples 79, 80, 81 can be converted to a correspondingacid.

TABLE 15 Substituents on the pyrrole ring Ex. in (1 h) No. R¹ R² R³ R⁴160. CH₃ H H Phenyl Mol. Wt. = 391 Yield = 59% 161. CH₃ H H Phenyl Mol.Wt. = 391 Yield = 25% E-isomer ¹H: 1.35(3H, t, J=6.8Hz); 2.36(3H, s);3.8–3.9(4H, m); 4.28(2H, t, J=6.4Hz); 5.5(1H, s); 5.9(1H, d, J=3.3Hz);6.0(1H, d, J=3.3Hz); 6.5(2H, d, J=8.7Hz); 7.1(2H, d, J= 8.6Hz);7.3–7.4(5H, m). 162. CH₃ H H Phenyl Mol. Wt. = 391 Yield = 25% Z-isomer¹H: 1.37(3H, t, J=7.0Hz); 2.3(3H, s); 3.9–4.02(4H, m); 4.3(2H, t,J=6.4Hz); 5.9(1H, d, J=3.2Hz); 6.1(1H, d, J=3.2Hz); 6.6(2H, d, J=8.8Hz);7.0(1H, s); 7.26–7.42(5H, m); 7.6(2H, d, J=8.8Hz).

PREPARATION 18 (R/S)3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoicacid (Example 163)

Using the procedure similar to that described in Preparation 15, theracemic ester (Example 72) was hydrolysed to its corresponding acid.

TABLE 16 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ 163. CH₃ HH Phenyl Mol. Wt. = 393 Yield = 50% ¹H: 1.06(3H, t, J=6.9Hz); 2.3(3H,s); 2.75–2.84(2H, m); 3.15–3.25(1H, m); 3.5–3.6(1H, m); 3.7(1H, m);3.88(2H, t, J=6.0Hz); 4.29(2H, t, J=6.0Hz); 5.8(1H, d, J=3.3Hz); 5.9(1H,d, J=3.3Hz); 6.53–6.56(2H, d, J=8.6Hz); 7.1(2H, d, J=8.6Hz);7.28–7.38(5H, m).

PREPARATION 19

Using the procedure similar to that described in Preparation 15, themethoxy and propoxy ester (Example 77 and 78) was hydrolysed to itscorresponding acid.

TABLE 17 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ R′ 164.CH₃ H H

CH₃ Mol. Wt. = 379 Yield = 20% — 165. CH₃ H H

C₃H₇ Mol. Wt. = 408 Yield = 22% —

PREPARATION 20 [2R, N(1S)]/[2S, N(1S)]2-Ethoxy-N-(2-hydroxy-1-phenylethyl)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}propanamide

To a well-stirred solution of (±) 2-ethoxy3-{4-[2-(5-Methyl-2-(4-methylphenyl)pyrrol-1-yl)ethoxy]phenyl}-propanoicacid (1 g, 2 mmole) (prepared as in Example no. 164) in drydichloromethane (10 mL), triethylamine (0.674 mL, 0.485 g, 4 mmole) wasadded at 0° C., followed by ethylchloroformate (0.311 g, 0.275 mL, 2mmole) and stirred for 3.5 hr at same temperature. To this reaction,solution containing of (S)-phenyl glycinol (0.329 g, 2 mmole) indichloromethane (5 mL) and triethylamine (0.674 mL, 0.485 g, 4 mmole)was added at 0° C. to 5° C. After stirring for 3 hrs at 0 to 10° C., thereaction was warmed to 20–25° C. and stirred for 16 hrs. The reactionmixture was diluted with dichloromethane (20 mL) and washed with H₂O (20mL), brine (20 mL), dried over anhy. Na₂SO₄ and evaporated.

The residue was chromatographed over silica gel using a gradient of10–50% of ethyl acetate:pet. ether as an eluent to afford firstlydiastereomer assigned as[(2R)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamideand[(2S)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide.

TABLE 18 Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ 166. CH₃ HH Phenyl Mol. Wt. = 407 Yield = 50% (2R) diastereomer ¹H: 1.12(3H, t,J=6.9Hz); 2.30(3H, s); 2.80–3.1(2H, dd); 3.5(2H, m); 3.91–3.95(5H, m);4.30(2H, t, J=6.5Hz); 5.00(1H, m); 5.90(1H, d, J=3.3Hz); 6.10(1H, d,J=3.3Hz); 6.60(2H, d, J=8.4Hz); 6.9–7.1(4H, m); 7.2–7.3(3H, m);7.32–7.4(5H, m). 167. CH₃ H H Phenyl Mol. Wt. = 407 Yield = 50% (2S)diastereomer ¹H: 1.18(3H, t, J=7.0Hz); 2.39(3H, s); 2.80–3.1(2H, dd);3.5–3.55(2H, m); 3.84–3.97(5H, m); 4.30(2H, t, J=6.7Hz); 5.00(1H, m);5.90(1H, d, J=3.3Hz); 6.10(1H, d, J=3.3Hz); 6.55(2H, d, J=8.6Hz);6.9–7.1(4H, d, J=8.5Hz); 7.22–7.26(3H, m) 7.41(5H, m).

PREPARATION 21(R)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoicacid from the corresponding diastereomer (Example No. 168)

A solution of[(2R)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide(Example no. 167)(280 mg, 0.546 mmole) in a mixture of 1M. sulfuric acid(7 mL) and dioxane: H₂O:HCl (1:1:56 mL) was heated for at 100° C. for 24hrs. The reaction mixture was cooled to 20° C. to 30° C. Product wasextracted in ethyl acetate (2×30 mL). Combined extract was washed withH₂O (3×30 mL), brine (30 mL) and dried over anhy. Na₂SO₄. Ethyl acetatewas evaporated under reduced pressure to afford (252 mg) product.

PREPARATION 22(S)-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoicacid from the corresponding diastereomer(Example No. 169)

A solution of[(2S)-N(1S)]-2-Ethoxy-3-{4-[2-(5-methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-N-(2-hydroxy-1-phenylethyl)propanamide (Example no. 168) was treated same as in preparation 20 toobtain the corresponding optically active acid. This was found identicalto that obtained in (Example no. 90).

PREPARATION 233-{4-[2-(5-Methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxypropanoicacid sodium salt (Example 170)

The acid prepared in example 90 (2.6 g) was dissolved in methanol (30mL), sodium hydroxide (0.264 g) was added and stirred for 1 hour at 20°C. to 25° C. Afterwards, methanol was distilled at reduced pressure, toobtain an oily product. It was stirred with diisopropyl ether (50 mL) at20–30° C. Solid sodium salt obtained was carefully filtered (2.3 g).

PREPARATION 243-{4-[2-(5-Methyl-2-phenylpyrrol-1-yl)ethoxy]phenyl}-2-ethoxy propanoicacid calcium salt (Example 171)

The sodium salt of example 170 (0.200 g), was dissolved in methanol (10mL) and treated with calcium acetate (0.090 g) at 20° C.–25° C. Further,50 mL of water was added when the calcium salt of the acid precipitatesout. The precipitate was filtered, washed with water and then withdi-isopropyl ether (2×20 mL) to afford the title compound.

Using the above procedure for Example 170 and Example 171 followingsalts are prepared using the appropriate acids/bases or according to themethods known in literature.

TABLE 19 (I)

M Ca⁺⁺ salts Substituents on the pyrrole ring in (I) Na⁺ salts ExampleR¹ R² R³ R⁴ n Example no. no. CH₃ H CH₃ H 2 172. 173. C₂H₅ H H H 2 174.175. CHO H H H 2 176. 177. COCH₃ H H H 2 178. 179. CH₃ H H CH₂CH₃ 2 180.181. CH₃ H H (CH₂)₂CH₃ 2 182. 183. CH₃ H H (CH₂)₃CH₃ 2 184. 185. CH₃ H H

2 186. 187. CH₃ H H

2 188. 189. CH₃ H H

2 190. 191. CH₃ H H

2 192. 193. CH₃ H H

2 194. 195. CH₃ H H

2 196. 197. CH₃ H

H 2 198. 199. CH₃ H

2 200. 201. i-Pr H H i-Pr 2 202. 203. i-Pr H H

2 204. 205. i-Pr

H

2 206. 207. SCH₃ H H H 2 208. 209. C₂H₅ H H C₂H₅ 2 210. 211. C₂H₅ H HC₆H₅ 2 212. 213. CH₃ H H

2 214. 215. CH₃ H H

2 216. 217. CH₃ H H

2 218. 219. CH₃ H H

2 220. 221. CH₃ H H

2 222. 223. CH₃ H H

2 224. 225. CH₃ H H

2 226. 227. CH₃ H H

2 228. 229. CH₃ H H

2 230. 231. CH₃ H H

2 232. 233. CH₃ H H

2 234. 235. CH₃ H H

2 236. 237. CH₃ H H

2 238. 239. CH₃ H H

2 240. 241. CH₃ H H

2 242. 243. CH₃ H H

2 244. 245. CH₃ H H

2 246. 247. CH₃ H H

2 248. 249. CH₃ H H

2 250. 251. COPh H H H 2 252. 253. CH₃ H H

2 254. 255. CH₃ H H

2 256. 257. CH₃ H H

2 258. 259. CH₃ COOCH₃ H

2 260. 261. CH₃ COOH H

2 262. 263. CH₃ H H

2 264. 265. CH₃ H H

2 266. 267. CH₃ H H

3 268. 269. CH₃ H H

2 270. 271. CH₃ H H

2 272. 273. CH₃ H H

2 274. 275. CH₃ H H

2 276. 277. CH₃ H CH₃

278. 279. CH₃ H H

2 280. 281. CH₃ H H

2 282. 283. CH₃ H H

2 284. 285. H H H

2 286. 287. CH₃ H H

2 288. 289. CH₃ H H

2 290. 291. CH₃ H H

2 292. 293. CH₃ CH₃ H C₆H₅ 2 294. 295. CH₃ H H

2 296. 297. H H H H 2 298. 299. CH₃ H H CH₃ 2 300. 301. i-Pr

H i-Pr 2 302. 303. i-Pr H H

2 304. 305. i-Pr H H

2 306. 307. i-Pr H

2 308. 309. i-Pr

2 310. 311.

—H H

2 312. 313.

—COOEt H

2 314. 315. i-Pr H H CH₃ 2 316. 317.

TABLE 20 (I)

M Substituents on the pyrrole ring in (I) Na⁺ salts Ca⁺⁺ salts R¹ R² R³R⁴ N Example no. Example no. CH₃ H H

2E-isomer 318. 319. CH₃ H H

2Z-isomer 320. 321.

TABLE 21 (I)

Ex. Substituents on the pyrrole ring No. R¹ R² R³ R⁴ R′ M 322. CH₃ H H

CH₃ Na Mol. Wt. = 401 Yield = 100% ¹H: 2.37(3H, s); 2.93–3.03(2H, m);3.37(3H, s); 3.90–3.96(3H, m); 4.28(2H, t, J=6.57 Hz); 5.96(1H, d,J=3.33Hz); 6.10(1H, d, J=3.36Hz); 6.61(2H, d, J=8.58Hz); 7.08 (2H, d,J=8.55Hz); 7.26–7.41(5H, m). 323. CH₃ H H

CH₃ Ca Mol. Wt. = 796 Yield = 44% ¹H: 0.83(3H, t, J=7.4Hz); 0.89(3H, t,J=7.4Hz); 1.53–1.63(4H, m); 2.37(3H, s); 2.91(2H, d, J=5.54Hz);3.20–3.48(2H, m); 3.92(6H, t, J=6.59Hz); 4.06(2H, t, J= 6.67Hz);4.28(2H, t, J=6.61Hz)5.97(1H, d, J=3.33Hz); 6.11(1H, d, J=3.40Hz); 6.59(2H, d, J=8.64Hz); 7.07(2H, d, J=8.63Hz); 7.25–7.40(5H, m). 324. CH₃ H H

C₃H₇ Ca Mol. Wt. = 852 Yield = 42% ¹H: 0.77(3H, t, J=7.41Hz);1.47–1.49(4H, m); 2.34(3H, s); 2.60–2.63(2H, s) 3.07– 3.38(2H, m);3.90(2H, t, J=6.01Hz); 4.31(2H, t, J=6.61Hz)5.87(1H, d, J=3.36Hz);5.99(1H, d, J=3.39Hz); 6.58(2H, d, J=8.52Hz); 7.10(2H, d, J=8.52Hz);7.29–7.40 (5H, m).

The compounds of the present invention lowered triglyceride, totalcholesterol, LDL, VLDL and increased HDL and lowered serum glucoselevels. This was demonstrated by in vivo animal experiments.

A) Demonstration of in Vitro Efficacy of Compounds:

i) Determination of hPPARα Activity:

A chimeric expression vectors constructs containing the translationalsequences of PPAR and amino acid sequences of DNA binding domains werefused and inserted into PGL3 basic vector. The expression and sequencewere verified through immunobloting and sequence analysis (ABI DNAanalyzer). These chimeric vectors containing ligand binding as well asDNA binding domain and a reporter plasmid containing the luciferase genedriven by SV40 promoter were transfected into CV-1 cell using thetransfectin (Gibco BRL, USA). A control reporter plasmid was alsotransfected to monitor the transfection efficiency. After 48 hrs oftransfection, The test compound was added in various concentration andincubated overnight. The luciferase activity was analyzed as a functionof compound binding/activation capacity of PPARα, by luciferase assaysystem (promega, USA).

ii) Determination of hPPARγ Activity:

A chimeric expression vectors constructs containing the translationalsequences of PPARγ and amino acid sequences of DNA binding domains werefused and inserted into PGL3 basic vector. The expression and sequencewere verified through immunobloting and sequence analysis (ABI DNAanalyzer). These chimeric vectors containing ligand binding as well asDNA binding domain and a reporter plasmid containing the luciferase genedriven by SV40 promoter were transfected into CV-1 cell using thetransfectin (Gibco BRL, USA). A control reporter plasmid was alsotransfected to monitor the transfection efficiency. After 48 hrs oftransfection, The test compound was added in various concentration andincubated overnight. The luciferase activity was analyzed as a functionof compound binding/activation capacity of PPARγ, by luciferase assaysystem (promega, USA).

B) Demonstration of in Vivo Efficacy of Compounds:

i) Serum Triglyceride and Total Cholesterol Lowering Activity in SwissAlbino Mice:

Male Swiss albino mice (SAM) were bred in Zydus animal house. All theseanimals were maintained under 12 hour light and dark cycle at 25±1° C.Animals were given standard laboratory chow (NIN, Hyderabad, India) andwater ad libitum. SAM of 20–30 g body weight range were used.

The test compounds were administered orally to Swiss albino mice at0.001 to 50 mg/kg/day dose for 6 days. The compound was administeredafter suspending it in 0.25% CMC or dissolving it in water, whencompound is water-soluble. Control mice were treated with vehicle (0.25%of Carboxymethylcellulose; dose 10 ml/kg).

The blood samples were collected on 0^(th) day and in fed state 1 hourafter drug administration on 6^(th) day of the treatment. The blood wascollected in non heparinised capillary and the serum was analyzed fortriglyceride and total cholesterol (Wieland, O. Methods of Enzymaticanalysis. Bergermeyer, H., O., Ed., 1963. 211–214; Trinder, P. Ann.Clin. Biochem. 1969. 6:24–27). Measurement of serum triglyceride andtotal cholesterol was done using commercial kits (Zydus-Cadila,Pathline, Ahmedabad, India).

Formula for Calculation:

Percentage reduction in triglycerides/total cholesterol were calculatedaccording to the formula:

$\text{Percentage~~reduction~~(\%)} = {1 - {\left\lbrack \frac{{TT}/{OT}}{{TC}/{OC}} \right\rbrack \times 100}}$

-   -   OC=Zero day control group value OT=Zero day treated group value    -   TC=Test day control group TT=Test day treated group

TABLE 1 Triglyceride lowering activity in Swiss albino mice: Dose %Triglyceride Example No. (mg/kg/day) lowering 76 3 26 287 3 54 257 3 55231 3 57

ii) Cholesterol Lowering Activity in Hypercholesterolemic Rat Models

Male Sprague Dawley rats stock bred in Zydus animal house weremaintained under 12 hour light and dark cycle at 25±1° C. Rats of100–150 g body weight range were used for the experiment. Animals weremade hypercholesterolemic by feeding 1% cholesterol and 0.5% sodiumcholate mixed with standard laboratory chow (NIN, Hyderabad, India) andwater ad libitum for 5 days. The animals were maintained on the samediet throughout the experiment [Petit D., Bonnefis M. T., Rey C andInfante R., Effects of ciprofibrate on liver lipids and lipoproteinsynthesis in normal and hyperlipidemic rats, Atherosclerosis, 74,215–225(1988)].

The test compounds were administered orally at a dose 0.03 to 50mg/kg/day for 4 days, after suspending it in 0.25% CMC or dissolving itin water when compound is water-soluble. Control group was treated withvehicle alone (0.25% of Carboxymethylcellulose; dose 10 ml/kg).

The blood samples were collected in fed state on 0^(th) and 1 hour afterdrug administration on 6^(th) day of the treatment. The blood wascollected from the retro-orbital sinus through non-heparinised capillaryand the serum samples were analyzed for triglyceride and totalcholesterol using commercial kits (Zydus-Cadila, Pathline, Ahmedabad,India). LDL and HDL by commercial kits (Point Scientific, USA). LDL andVLDL cholesterol were calculated from the data obtained for totalcholesterol, HDL and triglyceride.

The reduction in VLDL cholesterol is calculated according to theformula.VLDL cholesterol in mg/dl=Total cholesterol−HDL cholesterol−LDLcholesterol

TABLE 2 Dose Total cholesterol Example No. (mg/kg/day) reduction (%) 2273 59 118 3 53 277 3 62

iii) Serum Glucose Lowering Activity in db/db Mice Models

Homozygous animal C₅₇BL/KsJ-db/db mice are obese, hyperglycemic,hyperinsulinemic and insulin resistant (J. Clin. Invest., 85, 962–967,1990), whereas heterozygous are lean and normoglycemic. The homozygousanimals very closely mimic the human type II diabetes when blood sugarlevels are not sufficiently controlled. Since this type of modelresembles human type II diabetes mellitus, the compounds of theinvention were tested for their antidiabetic activity in this model.

The compounds of the present invention showed serum glucose andtriglycerides lowering activities. Male C₅₇ BL/KsJ-db/db mice of 8 to 14weeks age, having body weight range of 40 to 60 grams, procured from theJackson Laboratory, USA, were used in the experiment.

Test compounds were suspended on 0.25% carboxymethyl cellulose ordissolved in water when the compound is water soluble and administeredto test group containing 6 animals at a dose of 0.001 mg to 50 mg/kgthrough oral gavage daily for 6 days. The control group received vehicle(dose 10 ml/kg). On the 6^(th) day, one hour after the drug dosing,blood was collected from retro-orbital sinus and the serum was analyzedfor glucose and triglycerides were measured using commercial kits(Zydus-Cadila, Pathline, Ahmedabad, India). The serum glucose andtriglyceride lowering activities of the test compound was calculatedaccording of the formula:

${\text{Serum~~glucose~~lowering~~activity}\mspace{11mu}(\%)} = {1 - {\left\lbrack \frac{{TT}/{OT}}{{TC}/{OC}} \right\rbrack \times 100}}$Example Dose Serum Glucose Plasma TG No. (mg/kg/day) reduction (%)reduction (%) 259 1 62 11 283 1 67 27 OC = Zero day control group valueOT = Zero day treated group value TC = Test day control group TT = Testday control group

iv) Serum Triglyceride/Cholesterol/Body Weight Lowering Effect in GoldenSyrian Hamsters:

Male Golden Syrian hamsters were fed with a standard diet mixed with 1%cholesterol and 0.5% sodium cholate for 5 days. On 6^(th) day testcompounds in dose ranging from 1 mg to 10 mg/kg/day were administered asCMC suspension, and the same diet was maintained for the next 15 days.On the 15^(th) day the blood samples were collected in fed state, onehour after drug administration from retro-orbital sinus and the serumwas analyzed for triglyceride and cholesterol using commercial kits(Zydus-Cadila, Pathline, Ahmedabad, India). The body weight was measuredwith respect to untreated group on hypercholesteremic diet. Thecompounds of the present invention reduced triglycerides, cholesteroland body weight in this animal model.

No adverse effects were observed for any of the mentioned compounds ofinvention. The compounds of the present invention showed good serumglucose, lipid and cholesterol lowering activity in the experimentalanimals used. These compounds are useful for the testing/prophylaxis ofdiseases caused by hyperlipidemia, hypercholesterolemia,hyperinsulinemia, hyperglycemia such as NIDDM, cardiovascular diseases,stroke, hypertension, obesity since such diseases are interlinked toeach other.

1. The compound of formula (Ih),

wherein one or more groups R¹, R², R³, R⁴ may be same or different, andrepresent hydrogen, halogen, haloalkyl, perhaloalkyl, haloalkoxy,perhaloalkoxy, hydroxy, thio, amino, nitro, cyano, formyl, amidino,guanidino, or substituted or unsubstituted groups selected from linearor branched (C₁–C₁₂)alkyl, linear or branched (C₁–C₁₂)alkenyl, linear orbranched (C₁–C₁₂)alkynyl, (C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl,bicycloalkyl, bicycloalkenyl, (C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy,cyclo(C₃–C₇)alkoxy, aryl, aryloxy, aralkyl, ar(C₁–C₁₂)alkoxy,heterocyclyl, heteroaryl, heterocyclyl(C₁–C₁₂)alkyl,heteroar(C₁–C₁₂)alkyl, heteroaryloxy, heteroar(C₁–C₁₂)alkoxy,heterocycloxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,mono-substituted or di-substituted amino, arylamino, aralkylamino,carboxylic acid and its derivatives such as esters and amides,hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl,5 alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁–C₁₂)alkylthio,thio(C₁–C₁₂)alkyl, arylthio, (C₁–C₁₂)alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, alkyl hydrazino, alkoxyamino, hydroxyl amino, derivatives ofsulfenyl and sulfonyl groups, sulfonic acid and its derivatives,phosphonic acid and its derivatives; n represents an integer varyingfrom 1 to 8; W represents O, S or NR⁹, where R9 represents hydrogen,(C₁–C₁₂)alkyl or aryl groups; Ar represents a substituted orunsubstituted divalent single or fused aromatic, heteroaromatic or aheterocyclic group.
 2. A process for the preparation of compound offormula (Ih), as claimed in claim 1,

wherein one or more groups R¹, R², R³, R⁴ may be same or different, andrepresent hydrogen, halogen, haloalkyl, perhaloalkyl, haloalkoxy,perhaloalkoxy, hydroxy, thio, amino, nitro, cyano, formyl, amidino,guanidino, or substituted or unsubstituted groups selected from linearor branched (C₁–C₁₂)alkyl, linear or branched (C₁–C₁₂)alkenyl, linear orbranched (C₁–C₁₂)alkynyl, (C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl,bicycloalkyl, bicycloalketlyl, (C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy,cyclo(C₃–C₇)alkOxY, aryl, aryloxy, aralkyl, ar(C₁–C₁₂)alkoxy,heterocyclyl, heteroaryl, heterocyclyl(C₁–C₁₂)alkyl,heteroar(Cl—C₁2)alkyl, heteroaryloxy, heteroar(Cl—C₁₂)alkoxy,heterocycloxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,mono-substituted or di-substituted amino, arylamino, aralkylamino,carboxylic acid and its derivatives such as esters and amides,hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl,alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁–C₁₂)alkylthio,thio(C₁–C₁₂)alkyl, arylthio, (C₁–C₁₂)alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarboflylamiflo, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, alkyl hydrazino, alkoxyamiflo, hydroxyl amino, derivatives ofsulfenyl and sulfonyl groups, sulfonic acid and its derivatives,phosphonic acid and its derivatives; n represents an integer varyingfrom 1 to 8; W represents O, S or NR⁹, where R represents hydrogen,(C₁–C₁₂)alkyl or aryl groups; Ar represents a substituted orunsubstituted divalent single or fused aromatic, heteroaromatic or aheterocyclic group, which comprises, a. reacting a compound of thegeneral formula (Ic)

wherein one or more groups R¹, R², R³, R⁴ may be same or different, andrepresent hydrogen, halogen, haloalkyl, perhaloalkyl, haloalkoxy,perhaloalkoxy, hydroxy, thio, amino, nitro, cyano, formyl, amidino,guanidino, or substituted or unsubstituted groups selected from linearor branched (C₁–C₁₂)alkyl, linear or branched (C₁–C₁₂)alkenyl, linear orbranched (C₁–C₁₂)alkynyl, (C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl,bicycloalkyl, bicycloalkenyl, (C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy,cyclo(C₃–C₇)alkoxy, aryl, aryloxy, aralkyl, ar(C₁–C₁₂)alkoxy,heterocyclyl, heteroaryl, heterocyclyl(C₁–C₁₂)alkyl,heteroar(C₁–C₁₂)alkyl, heteroaryloxy, heteroar(C₁–C₁₂)alkoxy,heterocycloxy, heterocyclylalkyl oxy, acyl, acyloxy, acylamino,mono-substituted or di-substituted amino, arylamino, aralkylamino,carboxylic acid and its derivatives such as esters and amides,hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl,alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁–C₁₂)alkylthio,thio(C₁–C₁₂)alkyl, arylthio, (C₁–C₁₂)alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, alkyl hydrazino, alkoxyamino, hydroxyl amino, derivatives ofsulfenyl and sulfonyl groups, sulfonic acid and its derivatives,phosphonic acid and its derivatives; n represents an integer varyingfrom 1 to 8; and L¹ is either a halogen atom such as chlorine, bromineor iodine or a leaving group such as methanesulfonate,trifluoromethanesulfonate and p-toluenesulfonate groups, with a compoundof general formula (Ij), where Ar is as defined earlier;HO—Ar—CHO  (Ij) b. reacting a compound of the formula (Ie), withcompound of the formula (Ik), where L² is a halogen atom such asfluorine, chlorine, bromine or iodine and Ar is as defined earlier,

wherein one or more groups R¹, R², R³, R⁴ may be same or different, andrepresent hydrogen, halogen, haloalkyl, perhaloalkyl, haloalkoxy,perhaloalkoxy, hydroxy, thio, amino, nitro, cyano, formyl, amidino,guanidino, or substituted or unsubstituted groups selected from linearor branched (C₁–C₁₂)alkyl, linear or branched (C₁–C₁₂)alkenyl, linear orbranched (C₁–C₁₂)alkynyl, (C₃–C₇)cycloalkyl, (C₃–C₇)cycloalkenyl,bicycloalkyl, bicycloalkenyl, (C₁–C₁₂)alkoxy, (C₁–C₁₂)alkenoxy,cyclo(C₃–C₇)alkoxy, aryl, aryloxy, aralkyl, ar(C₁–C₁₂)alkoxy,heterocyclyl, heteroaryl, heterocyclyl(C₁–C₁₂)alkyl,heteroar(C₁–C₁₂)alkyl, heteroaryloxy, heteroar(C₁–C₁₂)alkoxy,heterocycloxy, heterocyclylalkyloxy, acyl, acyloxy, acylamino,mono-substituted or di-substituted amino, arylamino, aralkylamino,carboxylic acid and its derivatives such as esters and amides,hydroxyalkyl, aminoalkyl, mono-substituted or di-substituted aminoalkyl,alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, (C₁–C₁₂)alkylthio,thio(C₁–C₁₂)alkyl, arylthio, (C₁–C₁₂)alkoxycarbonylamino,aryloxycarbonylamino, aralkyloxycarbonylamino, aminocarbonylamino,alkylaminocarbonylamino, alkylamidino, alkylguanidino, dialkylguanidino,hydrazino, alkyl hydrazino, alkoxyamino, hydroxyl amino, derivatives ofsulfenyl and sulfonyl groups, sulfonic acid and its derivatives,phosphonic acid and its derivatives; n represents an integer varyingfrom 1 to 8; W represents O, S or NR1, where R1 represents hydrogen,(C₁–C₁₂)alkyl or aryl groups; with the proviso that: i. R¹, R² it³, it′all does not represent hydrogen atom at the same time, irrespective ofwhat n is; ii. R⁴ does not represent SO₂CH₃, when R1=H or COCH₃; R² andR³=H; and n=2; iii. R⁴ does not represent CHO, when R¹, R² and R³=H; andn=2; iv. R¹ does not represent NO₂, when R² and R³ H; R⁴=acyl; and n=2;v. R² and R³ does not represent hydrogen, when R¹ and R⁴ both aremethyl; and n=2 to 5; vi. R² and R³ does not represent hydrogen, when R′is methyl; R⁴ is nonaryl; and n=1 and 2; vii. R² and R³ does notrepresent hydrogen, when R1 and R⁴ are same or different substituentsselected the group such as NO₂, SO₂, CN, OMe, Halogen, COOH, COOR, SO₂R,SO(OR), SOR, PO(OR)₂, SR and n=1 to 8; viii. R⁴ does not representCH₂COOCH₃, when R¹=H; R² is either of hydrogen, lower alkyl [C₁–C₄,straight chain] or halide; R³ is either of hydrogen or COOCH₃ and n=2 to4; ix. R¹, R³ and R⁴ does not represent hydrogen at a time when R² isunsubstituted phenyl or phenyl substituted with halogen, methyl,trifluoromethyl, OMe, SMe; and n=1; x. R¹ and R⁴ does not representhydrogen at a time, when R² is unsubstituted phenyl or phenylsubstituted with halogen, methyl trifluoromethyl, OMe, SMe; R³ is CN,and n=1 to 9; xi. R¹ and R³ does not represent hydrogen at a time, whenR² is halogen; R³ is C(O)CO₂Et, CH(OH)CO₂Et and CH₂OOH₃, and n=2; xii.R¹, R² and R³ does not represent hydrogen at a time, when R³ is eitherof CH₂CN or CH₂NCH₃, and n=2; xiii. R² does not represent hydrogen, whenR¹ is phenyl or 3,4-dimethoxyphenyl, and R³ is either hydrogen, COOH orCOOEt, and R⁴ is methyl; and n=2 or 3; xiv. R³ and R⁴ does not representhydrogen, when R¹ is hydrogen; R² is unsubstituted benzyl ormonofluorobenzyl; and n=1; and R² and R³ does not represent hydrogen,when R³ and R⁴ are both alkyl; and n=1.